“In prior studies we found there are intrinsic differences among melanomas in their ability to metastasize or spread. Some are efficient metastasizers that readily form distant tumors whether you take them out surgically or not, while others are inefficient metastasizers that spread more slowly and that can be cured through surgery,” said Dr. Sean Morrison, Director of CRI and a Howard Hughes Medical Institute (HHMI) Investigator. “Since metastasis is a major determinant of clinical outcomes, we have focused for several years on understanding why some melanoma cells are better at it than others.”

Scientists have long known that most cancer cells die when they attempt to metastasize from a primary tumor to other parts of the body. Those that are able to survive during metastasis must undergo poorly understood metabolic changes.

A previous study conducted by the Morrison lab found one factor that limits the ability of melanoma cells to spread to other parts of the body is the high level of oxidative stress cancer cells experience during metastasis when they enter the bloodstream. Recently, another study at CRI in Dr. Ralph DeBerardinis’ lab found that more aggressive lung cancer cells consume higher levels of lactate. Based on these findings, scientists in the two labs hypothesized that some melanoma cells might be better at metastasizing if they were better at consuming lactate.  

To test this hypothesis, researchers used techniques developed by the Morrison laboratory for studying the metastasis of human melanoma cells in specialized mice and techniques developed by the DeBerardinis lab to label and track the use of nutrients in tumors. The researchers discovered that efficient metastasizers take up more lactate because they have higher levels of a lactate transporter on their cell surface, called monocarboxylate transporter 1 (MCT1), as compared with inefficient metastasizers.

Researchers involved in the study include (from left) Drs. Brandon Faubert, Alpaslan Tasdogan, Sean Morrison, and Ralph DeBerardinis.

“Efficient metastasizers are able to take up more lactate, which allows them to increase their production of antioxidants that help them to survive in the blood,” said Dr. Alpaslan Tasdogan, lead author of the study and a postdoctoral researcher in the Morrison lab. “The findings in our paper, along with those made previously by the DeBerardinis lab, strongly suggest that increased lactate uptake by cancer cells promotes disease progression. This correlates with clinical data showing that patients with higher levels of MCT1 in their cancers have worse outcomes.”

In the study, published in Nature, melanomas growing in mice that were treated with an MCT1 inhibitor led to fewer melanoma cells in the blood and fewer metastatic tumors. These data raise the possibility that MCT1 inhibitors, if given to patients before their cancer spreads, could reduce the proportion of patients who develop distant metastases, which are associated with systemic disease and much less likely to be curable.

“This paper makes a compelling case for analyzing metabolism in tumors,” said Dr. DeBerardinis, Professor at CRI and an HHMI Investigator. “It’s a great example of how assessing tumor metabolism can identify differences that correlate with cancer aggressiveness. Then you can identify an activity related to metastasis, inhibit it with a drug, and reduce metastasis in the mouse. That’s remarkable.”

Dr. Morrison is a Professor of Pediatrics at UT Southwestern, a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, and a member of the National Academy of Medicine. He also holds the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children’s Research Institute at UT Southwestern and Mary McDermott Cook Chair in Pediatric Genetics.

Dr. DeBerardinis is a Professor of Pediatrics at UT Southwestern, where he is Chief of the Division of Pediatric Genetics and Metabolism and holds the Joel B. Steinberg, M.D. Chair in Pediatrics and is a Sowell Family Scholar in Medical Research. He is also affiliated with the Eugene McDermott Center for Human Growth and Development and the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. At CRI, Dr. DeBerardinis is the Director of the Genetic and Metabolic Disease Program and is a Robert L. Moody, Sr. Faculty Scholar.

Dr. Tasdogan is a German National Academy of Sciences Leopoldina Postdoctoral Fellow.

The National Institutes of Health, HHMI, CPRIT, the Robert A. Welch Foundation, and donors to the Children’s Medical Center Foundation supported this work.

 About CRI

Children’s Medical Center Research Institute at UT Southwestern (CRI) is a joint venture of UT Southwestern Medical Center and Children’s Medical Center Dallas, the flagship hospital of Children’s Health. CRI’s mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology and metabolism. For more information, visit: cri.utsw.edu. To support CRI, visit: give.childrens.com/about-us/why-help/cri/

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

Payal Kapur, M.D.

“Clear cell renal cell carcinoma is the poster child of tumor heterogeneity as multiple, different populations of cells with different methods of behavior can be found in any particular tumor,” says Payal Kapur, M.D., a professor of pathology and urology at UT Southwestern, co-leader of pathology for the Kidney Cancer Program, and a co-author of the study. “Some of these cells develop aggressive traits and spread whereas others do not really progress, and it can be quite different from patient to patient.”

In the years since the Human Genome Project, technologies for deciphering the genetic code have vastly improved, enabling scientists to decode the genetic sequence of individual patients and their tumors. While much knowledge has been gleaned from this type of research, this approach has not reached clinical practice as it is expensive and requires specific expertise, says Qi Cai, M.D., Ph.D., an assistant professor of pathology and first author of the study.

Using tissue staining techniques that have been widely used for more than a century, Kapur and her team analyzed tumor samples from 549 patients. Specifically, they characterized how the cells are arranged within the tumor, what each individual cell looks like and how the tumor interacts with the surrounding tissue. They measured 33 parameters that they defined within these three categories. Then, to see if these tumors were able to grow in a foreign site, the team implanted tiny tumor samples into the kidneys of mice.

Illustration of the nine distinct patterns of ccRCC morphology based on extensive analysis of tumor architecture, cytology, and microenvironment. Thirty three cancer cell variables were defined which were then grouped into these nine patterns. This enabled the identification of aggressive phenotypes and shed light on tumor evolution.

Analyzing information about drug treatments the patients had received and how well they worked, the researchers were able to associate specific tumor characteristics with the drugs that worked best against those types of cells. “Most medicines for metastatic kidney cancer today do not directly act on tumor cells,” explained James Brugarolas, M.D., Ph.D., a professor of internal medicine, Director of the Kidney Cancer Program, and a co-author of the study. “Thus, it is not surprising that information about the tumor neighborhood could inform treatment response.”

Kapur and her team of experts in artificial intelligence, data analytics, oncology, and radiology have developed the first comprehensive catalog of ccRCC and an evolutionary model. By analyzing tumor composition (how the different subtypes occur together in individual patient tumors) across tumors of different size and grade, the team was able to develop an evolution trajectory of ccRCC progression, says Satwik Rajaram, Ph.D., an assistant professor of bioinformatics and pathology in the Lyda Hill Department of Bioinformatics, the Center for Alzheimer’s and Neurodegenerative Diseases, and a co-author of the study.

“This remarkable team with expertise across a broad array of fields has provided unique insight into ccRCC,” says Brugarolas. “This type of innovative approach illustrates how we continue to learn more about, tailor treatments to, and improve patient outcomes for kidney cancer here at UTSW.”

Payal Kapur holds the Jan and Bob Pickens Distinguished Professorship in Medical Science, in Memory of Jerry Knight Rymer and Annette Brannon Rymer and Mr. and Mrs. W.L. Pickens

James Brugarolas holds The Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D.

Additional study authors are Alana Christie, Qinbo Zhou, Ellen Araj, Suneetha Chintalapati, Jeffrey Cadeddu, Vitaly Margulis, Ivan Pedrosa, Dinesh Rakheja, Renee McKay, all of UT Southwestern.

This research was funded by Cancer Prevention and Research Institute of Texas (CPRIT) grant RP130603, National Institutes of Health (NIH) grant P50CA196516, and an endowment from Brock Fund for Medical Science Chair in Pathology and the Jan and Bob Pickens Distinguished Professorship in Medical Science. The UT Southwestern Kidney Cancer Program is supported by the National Cancer Institute (NCI) through a Specialized Program of Research Excellence (SPORE) award and by CPRIT.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – Dec. 10, 2019 – Federal regulations may keep lung cancer patients out of clinical trials simply because these patients are on medications that might affect the electrical system of the heart. Drilling into the details quickly turns up reasons to think these regulations may be preventing a substantial proportion of patients from participating in clinical trials. There may be alternatives, and researchers and physicians should explore them.

These are the conclusions of a team of researchers from UT Southwestern Medical Center that included members of the Harold C. Simmons Comprehensive Cancer Center. Their findings, published in the journal Clinical Lung Cancer in November, might help break down barriers for patients to participate in important, potentially lifesaving clinical trials. The barriers currently exclude thousands of patients.

“This issue comes up all the time in my practice,” said Dr. David Gerber, who treats lung cancer patients and is a Professor of Internal Medicine and Population and Data Sciences. He is one of the study’s authors and has been studying clinical trial eligibility criteria for a decade.

Clinical trial eligibility criteria are designed to limit risks to study participants. But, according to Dr. Gerber, these criteria may be excessive in places.

“The criteria are not as thoughtful as they could be,” Dr. Gerber said. “We keep cutting and pasting from earlier studies, basically doing the same things over and over without justifying them or deciding if they’re rational.”

Using a database of more than 280,000 Veterans Health Administration patients with lung cancer, the study found that more than 25 percent of lung cancer patients were prescribed medications with potential cardiac risk, and almost 10 percent were taking multiple such medications. Dr. Gerber noted that even if these medications are not having cardiac effects on patients, simply receiving the medications may bar patients from clinical trials. Furthermore, when cardiac effects are noted, the actual risk to patients is often measured over a 40-year period. Because most lung cancer patients are over 70 years old, a 40-year range of possible risks may be less relevant.

“Lung cancer is a serious and possibly life-threatening condition,” Dr. Gerber said. “When we design clinical trials, we need to consider potential benefits as well as theoretical risks.”

Dr. Carlos L. Arteaga, Director of the Simmons Cancer Center and Associate Dean of Oncology Programs, said studies like Dr. Gerber’s are urgently needed because less than 2 percent of adult cancer patients in the U.S. are enrolled in clinical trials that can benefit the patient and advance scientific knowledge. He said clinical trials for lung cancer are particularly important because lung cancer is the leading cause of cancer deaths in Texas and the nation.

“Studying barriers to clinical trials can be as important as creating a new clinical trial itself. Patients can’t benefit from trials they can’t access,” said Dr. Arteaga, also Professor of Internal Medicine who holds The Lisa K. Simmons Distinguished Chair in Comprehensive Oncology. “Dr. Gerber’s work is one of the first steps in making clinical trials more accessible.”

Dr. Mark Link, a cardiologist and Professor of Internal Medicine who worked on the study, said the seemingly excessive caution around the drugs stems largely from a medical crisis in the late 1990s. A new drug created to treat gastric motility disorders such as diarrhea, vomiting, and severe constipation showed positive effects on the gastrointestinal tract but serious threats to the heart.

“This new drug was widely used and very effective. It worked extremely well, but then the reports started coming in of QTc prolongation of this drug, and it was taken off the market,” said Dr. Link, who holds the Laurence and Susan Hirsch/Centex Distinguished Chair in Heart Disease.

QTc prolongation is the blip on an electrocardiogram, the iconic machine on the medical TV shows that charts each heartbeat with a beep and a fever chart line. The space between the highest peaks on the EKG line is known as the QTc interval. It is the moment the heart is preparing to beat again. It’s a crucial step in cardiac health – in staying alive – so the threats caused by the gastric motility disorder drug prompted the FDA to zero in on other drugs that affect QTc prolongation. The fallout included strict rules stating that patients taking drugs that prolong – or even might prolong – QTc intervals cannot enter clinical cancer trials.

The most common QTc-prolonging medications that the study found to be potential barriers to clinical trials included antibiotics, psychiatric medications, and cardiac medications.

Other researchers who contributed to the study were Dr. Tri Le, a hematology-oncology postdoctoral fellow; Dr. Sawsan Rashdan, Assistant Professor of Internal Medicine; Dr. Carlos Alvarez, Associate Professor of Population and Data Sciences; and Dr. Hui Yang, a Chief Analyst at Texas Tech University Health Science Center.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – Dec. 9, 2019 – UT Southwestern researchers have developed a software tool that uses artificial intelligence to recognize cancer cells from digital pathology images – giving clinicians a powerful way of predicting patient outcomes.

The spatial distribution of different types of cells can reveal a cancer’s growth pattern, its relationship with the surrounding microenvironment, and the body’s immune response. But the process of manually identifying all the cells in a pathology slide is extremely labor intensive and error-prone.

“As there are usually millions of cells in a tissue sample, a pathologist can only analyze so many slides in a day. To make a diagnosis, pathologists usually only examine several ‘representative’ regions in detail, rather than the whole slide. However, some important details could be missed by this approach,” said Dr. Guanghua “Andy” Xiao, corresponding author of a study published in EBioMedicine and Professor of Population and Data Sciences at UT Southwestern.

The human brain, Dr. Xiao added, is not good at picking up subtle morphological patterns. Therefore, a major technical challenge in systematically studying the tumor microenvironment is how to automatically classify different types of cells and quantify their spatial distributions, he said.

The AI algorithm that Dr. Xiao and his team developed, called ConvPath, overcomes these obstacles by using AI to classify cell types from lung cancer pathology images.

Here’s how it works: The ConvPath algorithm can “look” at cells and identify their types based on their appearance in the pathology images using an AI algorithm that learns from human pathologists. This algorithm effectively converts a pathology image into a “map” that displays the spatial distributions and interactions of tumor cells, stromal cells (i.e., the connective tissue cells), and lymphocytes (i.e., the white blood cells) in tumor tissue.

Whether tumor cells cluster well together or spread into stromal lymph nodes is a factor revealing the body’s immune response. So knowing that information can help doctors customize treatment plans and pinpoint the right immunotherapy.

Ultimately, the algorithm helps pathologists obtain the most accurate cancer cell analysis – in a much faster way.

“It is time-consuming and difficult for pathologists to locate very small tumor regions in tissue images, so this could greatly reduce the time that pathologists need to spend on each image,” said Dr. Xiao, who also has an appointment in the Lyda Hill Department of Bioinformatics and is a member of both the Quantitative Biomedical Research Center (QBRC) and the Harold C. Simmons Comprehensive Cancer Center at UTSW.

The ConvPath software – which incorporates image segmentation, deep learning, and feature extraction algorithms – is publicly accessible at https://qbrc.swmed.edu/projects/cnn/.

Dr. Guanghua “Andy” Xiao

The study’s lead authors include Shidan Wang, QBRC Data Scientist II; Dr. Tao Wang, Assistant Professor of Population and Data Sciences and in the Center for the Genetics of Host Defense; and Dr. Donghan M. Yang, QBRC Project Manager. Other co-authors from UT Southwestern include Dr. Yang Xie, Professor of Population and Data Sciences, a Professor in the Lyda Hill Department of Bioinformatics, and Director of the QBRC, and Dr. John Minna, Professor of Pharmacology and Internal Medicine and Director of the Hamon Center for Therapeutic Oncology Research. Dr. Minna holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology.

The study was supported by the National Institutes of Health and the Cancer Prevention and Research Institute of Texas.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – Nov. 20, 2019 – Juan Cueto did not feel sick, but he was losing weight rapidly and was devastated with the knowledge that he had two life threatening diseases, cancer and a liver disease.

Doctors in another state told him there was no treatment; only a liver transplant would cure him of the primary sclerosing cholangitis he was diagnosed with in 2012. He was told this liver disease could lead to bile duct cancer – and it did.

“It was very frustrating. I felt like, ‘How long do I have?’ You start thinking about your kids, your future. Your life is going down,” said Mr. Cueto, a 46-year-old electrical engineer who lives in Frisco.

Mr. Cueto’s prospects changed dramatically when he moved to Texas in 2016 and found a team of specialists at UT Southwestern who could address both issues in one surgery.

Dr. Parsia Vagefi brought the new surgical protocol for bile duct cancer and liver disease when he came to UT Southwestern in 2018 as Associate Professor of Surgery and the Ernest Poulos, M.D. Distinguished Chair in Surgery. The surgery protocol would give Mr. Cueto a new liver by transplant and surgically remove the bile duct. Of the 7,000 liver transplants that take place nationwide every year, only 1 percent address bile duct cancer in the same surgery.

Dr. Vagefi told Mr. Cueto, “It’s a little bit of a Hail Mary pass, but sometimes Hail Marys work.”

UT Southwestern had the expertise, but Mr. Cueto had to wait for a liver to become available. A man he knew suffered from a similar condition, and he was alarmed to see his health decline rapidly. The man was near death when he received a partial liver transplant from a living donor.

“That really scared me too,” said Mr. Cueto who has a teenage son and a daughter in college.

To be eligible for transplant, doctors would need to ensure that cancer had not spread anywhere else in his body. Oncologists from the Harold C. Simmons Comprehensive Cancer Center put Mr. Cueto on a carefully planned treatment plan of radiation and chemotherapy.

His medical oncologist, Dr. Muhammad Beg, said the careful monitoring that comes with every patient plan was particularly important for Mr. Cueto with scans receiving extra scrutiny.

“We monitor patients very closely with scans. Patients need to fit very specific criteria before they are considered for transplant. Part of this process is a detailed discussion of their scans in a multidisciplinary tumor board,” said Dr. Beg who is an Associate Professor of Internal Medicine and Dedman Family Scholar in Clinical Care. “We also ensure that chemotherapy and radiation is given following strict criteria and proven protocols.”

Dr. Vagefi said many patients in this situation nationwide do not make it to transplant because their cancer spreads. After imaging in Radiology, UT Southwestern doctors did an endoscopy to ensure cancer had not reached Mr. Cueto’s lymph nodes.

“There were a lot of people involved getting him to transplant,” Dr. Vagefi said. “It was a true multidisciplinary effort.”

In July, Mr. Cueto got the call. A liver had become available.

“I was super scared,” he said. “You have to be strong and hope for the best.”

Dr. Vagefi said the first phase of the surgery focused on making sure cancer had not spread elsewhere in Mr. Cueto’s body. Any sign of spread would halt the operation, he would not get a new liver, and he would be back to square one.

“We inspected the entire abdomen to make sure there is no evidence of microscopic spread, and we sampled certain lymph nodes that surround the liver,” Dr. Vagefi said. “We sent those to the Department of Pathology, another area of expertise that we have at UT Southwestern that helped contribute to this team effort. They look at those slides right away and they can tell us whether there is spread of the cancer or not. If there’s spread then we abort the case.”

Another potential recipient was ready, per the protocol’s requirement, to receive the liver if Mr. Cueto’s case was aborted. But one after another, the results came back. No cancer had spread. Dr. Vagefi moved on to the transplant and surgical removal of the bile duct.

“We cut out the recipient’s bile duct in its entirety. We didn’t want to leave any of that behind for the chance of harboring cancer or developing cancer in the future,” he said. “But we still needed a way to drain the donor liver bile duct so we had to reroute the bowl and connect it to the donor bile duct and allow it to drain. That added another level of complexity to the case.”

Dr. Vagefi said he found radiation oncologists had worked with tremendous precision; radiation treatments were tightly focused in a specific area. This meant that blood vessels were not radiated any more than necessary, leaving an ample amount of blood vessels for reconnection. No bypasses were needed. Veins, an artery, the new bile duct were delicately sutured in the surgery’s final steps.

Hours later Mr. Cueto woke up in the recovery room, and Dr. Vagefi came to his bedside. He was too groggy to remember Dr. Vagefi’s exact words, but he remembers him saying everything went well. He would have no restrictions going forward.

“I was so happy. It was like my second birthday,” Mr. Cueto said. “I feel like I was in the right place at the right time. It was a very professional team, very well organized.”

Blood tests and follow up appointments show Mr. Cueto enjoying a strong recovery. He looks forward to having his 21-year-old daughter home for the holidays and has begun building a vintage video game replica in the garage with his 15-year-old son.

“I feel great,” he said. “I felt like somebody was looking out for me, and they were making the best decisions for me. I didn’t have any doubt that I was in the right place at the right time.”

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – Oct. 29, 2019 – Sandra McKinney grew so attached to the Simmons Cancer Center at UT Southwestern that she decided to fly back for follow-up appointments instead of finding a new provider when she moved to New Jersey.

“The people are kind. The nursing staff is really kind,” she said. “I just felt like I could never be anything but joyous that I was there.”

The 59-year-old mother of two said she discovered a lump in her breast in January 2017. After visiting a local hospital, she received a phone call with a diagnosis of triple negative breast cancer.

“She told me I needed to find a surgeon and good luck and hung up the phone,” Mrs. McKinney said.

Triple negative breast cancer is particularly aggressive and challenging because it lacks the three hormones that oncologists typically use as a foothold for cancer treatments.

“I thought, ‘I’m going to do this, and I’m going to have a sweet attitude because I can control that,’” she said. “From the very start, I told my husband I was going to be kind and happy, and I was going to be the best patient they ever had.”

At the Harold C. Simmons Comprehensive Cancer Center Mrs. McKinney said she met people who shared her positive attitude and focus on what can be done.

“I felt relief because I felt like I’d found my people,” she said.

People like her oncologist Dr. Nisha Unni, a physician-researcher who is conducting clinical trials on breast cancer and triple negative breast cancer. Dr. Unni is working to identify with a much higher level of specificity how effective chemotherapy is and which patients are best suited for it. By delivering chemotherapy before – instead of after – surgery, she can analyze surgically removed tumors down to the molecular level. It’s a forward-looking approach paving the way for future treatments.

Mrs. McKinney remained focused on the future not just for her, but for her family. She elected for genetic testing at UT Southwestern to learn what might be in store for her and her two adult children.

“I have a daughter, and I didn’t want her to be sitting in the chair I was sitting in. I wanted to know and be at peace with that,” she said.

The genetic testing revealed she lacks a gene for another type of breast cancer commonly associated with triple negative breast cancer, but she has a variant of uncertain clinical significance for a gene for colon cancer. She shared the news with her children immediately, and they adopted regular screenings.

Now Mrs. McKinney looks forward to the upcoming weddings of both her daughter and her son and hopes for grandchildren soon. She’s never been a nature person, but as a new chapter of life begins, she said she is pleasantly surprised how much she enjoys walks in a nature preserve near her home.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – Oct. 9, 2019 – On Wendy Casper’s first day at the Simmons Cancer Center at UT Southwestern she met a fellow breast cancer patient, a volunteer.

The woman said her treatment was done, but she came back as a volunteer because she missed the Harold C. Simmons Comprehensive Cancer Center.

“I thought, ‘Well, that’s weird. Who would want to go back?’ But I get it now. I go over to the Simmons Cancer Center, and I feel comforted,” Ms. Casper said.

The Simmons Cancer Center helped her beat breast cancer and continue her career as a Professor and Associate Dean in the College of Business at the University of Texas at Arlington.

On Friday, Ms. Casper’s last day of infusion chemotherapy, she enjoyed a surprise reunion with Mary Ellen Garland, the volunteer who helped her on her first day of treatment. When told that Ms. Garland was there to see her, Ms. Casper’s jaw dropped and eyes widened.

“Oh, my God!” she gasped, bringing her hand to her mouth. “I would love to see her!”

Ms. Garland entered, and the two women embraced in a hug that exemplified the support cancer survivors give each other and the bonds built at the Simmons Cancer Center.

“I get it now, what you said to me last year, when you said that you came back here,” Ms. Casper said as the two clasped hands. “I feel connected now to everybody that understands this journey, and everybody here has been so good to me – and it all started with that day I met you almost a year ago.”

“This is where health care is supposed to be,” Ms. Garland said with a wide smile.

“That’s definitely what I found. So many times I realized, I never had this kind of medical care before,” Ms. Casper said. “I never had this level of attention and care for my well-being.”

Ms. Garland said it meant a lot to hear that her volunteer work helped someone else, and that someone remembered her from her first, overwhelming day as a cancer patient.

“It’s always gratifying because you are in such a spin when you first have this happen,” she said. “You don’t remember anything. You just think, everybody’s nice, everybody’s trying to help you, so to be remembered specifically is very gratifying. … It is a very supportive environment. That is truly what I think this thing is all about.”

The reunion was a happy ending to Ms. Casper’s yearlong fight against cancer that came on suddenly. More than a decade of mammograms showed nothing, and Ms. Casper had no history of breast cancer in her family, so a diagnosis of breast cancer in late 2018 “came out of nowhere.”

A doctor in Tarrant County told her, “I hate to do this over the phone, but you have cancer.”

Staff at the first hospital she spoke with seemed less focused on her as a patient and more focused on the reconstructive breast surgery she would eventually need. She wanted a team that treated her differently from this. People kept recommending Dr. Marilyn Leitch, a breast surgeon at the Simmons Cancer Center. Dr. Leitch is a Professor of Surgery and holds the S.T. Harris Family Distinguished Chair in Breast Surgery, in Honor of A. Marilyn Leitch, M.D.

“Everyone kept saying this is the best breast surgeon,” she said. “The day I came to see her my life changed, and it was like, ‘Everything’s going to be ok.’ My anxiety was way down, and I just felt so much safer. I felt like everything was going to be ok.”

The doctors and staff focused on her as a person and moved to make her treatment as quick and easy as possible. She said she felt like a priority when she could hear the scheduler working the phones to advance her appointments.

“She kept saying, ‘Escalate, escalate. She’s a new diagnosis, she needs to get in right now.’ She was on the phone doing that for like 40 minutes, and she got off the phone and had all these appointments for me,” Ms. Casper said. “I was just completely overwhelmed with gratitude.”

Wendy Casper and her husband Roger Duval

Ms. Casper’s husband, Roger Duval, said he also noticed how attentive the entire team was.

“They made sure we were introduced to the nurses,” he said. “There was just this complete package feeling that we were definitely with competent people who were totally focused on your needs. Every single individual we interacted with has been focused and competent and careful.”

Ms. Casper had chemotherapy, radiation, and surgery to treat the cancer. She temporarily lost her hair to chemotherapy but did not get the mental fogginess of “chemobrain” – a side effect that she feared would interfere with her scholarly work as a professor.

She said the cancer team helped her with each step of treatment.

“People have just taken care of me in a way that I had never experienced before in the medical system,” she said. “It really helped keep my spirit up. I really felt like I had really been cared for as a human being.”

Ms. Garland was part of that, and she was there at the beginning – as an example of someone giving back. Ms. Casper said she is already at work on her own way of giving back. Ms. Casper, who has a Ph.D. in organizational psychology, studies ways to improve the health and well-being of employees. She said she will now study how cancer patients in outpatient treatment juggle their schedule and cancer care.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

The study published today in Science Immunology suggests that giving the two therapies as short course, first-line treatment might work better than the current practice of providing one treatment early and the other treatment only if tumors relapse.

(l-r) Drs. Chuanhui Han, Yang-Xin Fu, and Zhida Liu

“This study reveals the importance of the proper combination and timing of tyrosine kinase inhibitors and immunotherapy such as the programmed death-ligand 1 (PD-L1) inhibitor, also known as immune checkpoint blockade. If borne out by future research, these findings might open new treatment avenues for many cancer patients,” said corresponding author Dr. Yang-Xin Fu, Professor of Pathology, Immunology, and Radiation Oncology and a member of the Harold C. Simmons Comprehensive Cancer Center.

“Many cancers have high and abnormal tyrosine kinase activities. Tyrosine kinase inhibitors, or TKIs – which target specific cancers – are a common first-line treatment for rapidly shrinking tumors such as those associated with kinase-driven breast cancer and lung cancer. But tumor relapse or resistance often occurs. The standard of care is to use TKIs first and then use immunotherapy such as PD-L1 inhibitors after relapse occurs,” Dr. Fu explained. “Our study showed that immunotherapy should be used together with the TKIs as the first-line – not second-line or third-line – treatment. We also demonstrated that the dose and timing of the TKI is important.”

The team, which included first authors and postdoctoral researchers Drs. Zhida Liu and Chuanhui Han, also found that hypofractionated TKI (HypoTKI) – giving a high dose over a short time – was more effective in mouse models of breast cancer and lung cancer than standard hyperfractionated TKI (HyperTKI) – lower doses over a longer time. Compared with standard therapy, the high-dose/short time TKI approach appeared to significantly reduce tumor burden and limit relapse with fewer side effects.

Earlier studies that found increased side effects when TKI and PD-L1 were given together had used HyperTKI rather than the HypoTKI provided in this investigation, said Dr. Fu, a physician-scientist who holds the Mary Nell and Ralph B. Rogers Professorship in Immunology.

The researchers found that TKIs work in part by activating both innate and adaptive immunity – that is, both of the body’s immune systems. The innate immune system is activated as soon as a threat is identified. Adaptive immunity is the body’s response to threats it has learned to recognize, Dr. Fu explained.

PD-L1 inhibitors are thought to enhance adaptive immunity to overcome the ability of some tumor cells to develop resistance to TKIs, he added.

Compared with standard HyperTKI therapy, the HypoTKI approach triggered greater innate immune sensing and a more potent release of type I interferon and other cytokines through an innate immunity signaling pathway to enhance tumor-specific T cell infiltration and reactivation. The researchers also found that HypoTKI was more potent than HyperTKI in limiting tumor relapse in a host immune response-dependent manner. More importantly, they observed that PD-L1 blockade could further enhance the anti-tumor effectiveness of HypoTKI treatment in advanced large tumors and limit the relapse. The timing of the dose of the drugs was important, he said.

The study is among the first to find that this class of TKIs can trigger the innate immune response, Dr. Fu said. “We think there might be a threshold effect with HypoTKI in which the treatment more effectively alerts the innate immune system. It appears that higher-dose/shorter duration TKI treatment may spark a more potent anti-tumor response by better triggering the innate immunity system.”

In one series of experiments, the researchers found that tumors were completely resistant to anti-PD-L1 therapy alone, so-called monotherapy. When HypoTKI was given by itself, it markedly reduced tumor burden initially, but all tumors relapsed eventually.

When the two treatments were given concurrently and early, it resulted in the best tumor regression and most mice showed no relapse over more than two months of follow-up. Tumor relapse in mice usually occurs within two to three weeks.

“The maximum synergistic effect of combination therapy depends on the timing of the anti-PD-L1 treatment. When it was started within three days of TKI administration, there was total tumor regression and only two of eight tumors relapsed,” Dr. Fu said.

Almost no synergistic effect was seen if PD-L1 inhibitors were provided a week after TKI therapy.

“Our study demonstrates that HypoTKI and PD-L1 blockade can work in combination to effectively control advanced large tumors, increase overall survival, and reduce tumor relapse. These data suggest that proper timing – giving the two agents together at the start of treatment – provides maximum synergistic anti-tumor effects in these tumors and should be studied further,” Dr. Fu said.

UTSW co-authors include Research Associate Dr. Chunbo Dong, Drs. Zhenhua Ren, Changzheng Lu, Longchao Liu, Anli Zhang, all postdoctoral researchers in the Fu laboratory; Eric Hsu and Casey Timmerman, both students in the Medical Scientist Training Program that grants dual M.D./Ph.D. degrees; Dr. Mingyi Chen, Associate Professor of Pathology; and Dr. Jian Qiao, Assistant Professor of Pathology. Former laboratory manager Yang Wang and former postdoctoral researchers Aijun Shen, and Yang Pu also participated.

The study received support from the National Institutes of Health and the Cancer Prevention and Research Institute of Texas (CPRIT).

The authors report no disclosures.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

The finding builds on a December 2018 study by the same researchers who found that antiviral drugs do not increase the risk of liver cancer recurrence, as was previously feared.

Dr. Amit Singal

Dr. Amit Singal’s study was published in the journal Gastroenterology on July 30. Dr. Singal is an Associate Professor of Internal Medicine, Medical Director of the UT Southwestern Liver Tumor Program, and Clinical Chief of Hepatology. He collaborated on these studies with Dr. Caitlin Murphy, Assistant Professor of Population and Data Sciences and Internal Medicine. They are both members of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

Their studies overturn prior misconceptions that made doctors reluctant to prescribe direct-acting antivirals to treat hepatitis C in patients with a history of liver cancer. Many doctors previously believed that hepatitis C, for all its harmfulness, activates the immune system when it infects the liver, and the immune system kept liver cancer recurrence at bay.

But this notion appears to be false. Drs. Singal and Murphy studied nearly 800 patients from 31 medical centers across the country and found that the drugs are not only safe, they decrease death from cirrhosis and liver cancer by 46%.

“Not only are these drugs safe in this patient population, but we have now demonstrated that they are helpful,” Dr. Singal said. “Our study changes the paradigm from you could treat a patient’s hepatitis C to you should treat it.”

Dr. Caitlin Murphy

Dr. Carlos L. Arteaga, Director of the Simmons Cancer Center, said the study’s scope and impact are something that can only be produced by a National Cancer Institute-designated Comprehensive Cancer Center.

“Dr. Singal had more patients involved in the study than any other participating site. As an epidemiologist, Dr. Murphy brought rigor to the data that removes prior doubt on this issue,” he said.

Dr. Murphy said previous studies compounded the misunderstandings of direct-acting antiviral therapy because they, among other things, failed to account for the timing of therapy relative to liver cancer diagnosis, did not include a comparison group, or did not properly consider clinical differences among patients.

The new study is a significant contribution because it clears the path to beneficial drug treatment.

“Hepatitis C therapy is so important because it provides a cure,” Dr. Singal said. “You take oral medications for two or three months, with minimal to no side effects, and you’re done. You’re cured of hepatitis C. There’s less than a 1% chance of relapse if you’re cured of hepatitis C.”

Defeating hepatitis C is an important step because infection can otherwise lead to cirrhosis – scarring of the liver – which can be deadly. Cirrhosis can increase the risk for liver cancer, which also may be fatal. Curing hepatitis C with antivirals breaks the first link in a deadly chain of events and can lead to improvement in liver function among those who have previously developed cirrhosis.

Hepatitis C rapidly made its way into the American blood stream in the 1970s and 1980s when intravenous drug use spiked and blood products were not screened for the hepatitis C virus. Hepatitis C infected 2 to 3% of the baby boomer population, the largest generation in U.S. history. Millions were affected.

The disease can lie dormant for 25 to 30 years and resurface as a life-threatening specter years after someone has stopped using drugs and turned to a healthy lifestyle. Hepatologists saw an alarming spike in cirrhosis as baby boomers aged. By 2017, The New York Times called hepatitis C “an enormous public health problem.” In 2018, the Centers for Disease Control and Prevention announced there were nearly 2.4 million people living with hepatitis C in the U.S.

“Dr. Singal’s and Dr. Murphy’s study reports a welcome, fact-based way to oppose the adverse effects of hepatitis C infection in various demographic groups,” Dr. Arteaga said. “Their findings will have a global, lifesaving impact on how hepatitis C is treated. It is particularly important to Texas because the liver cancer incidence rate in Texas is the highest in the nation.”

Dr. Arteaga said the study is also important because liver cancer is highest among the Hispanic population in Texas, and research-based advances in reducing cancer in underserved groups are a Simmons Cancer Center priority.

The Simmons Cancer Center stands among only 32 U.S. cancer research centers named by the National Cancer Institute as a National Clinical Trials Network Lead Academic Participating Site.

The authors declared financial interests with the manuscript.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – Aug. 5, 2019 – Dr. Woodring Erik Wright, Professor of Cell Biology, passionate educator, and scientific trailblazer in the fight against aging and cancer, died on Aug. 2. He was 70.

A faculty member since 1978, Dr. Wright dedicated decades of research to studying the relationships between aging and cancer and focused on the role of the end caps of chromosomal DNA, called telomeres, in these processes.

Together with longtime collaborator Dr. Jerry Shay, Dr. Wright explored molecular mechanisms that regulate telomere shortening and telomerase activity. The laboratory partners leveraged these mechanistic insights into studies on how telomere shortening contributes to human aging and pursued a variety of approaches to transform their insights to develop treatments for cancer and age-related diseases.

“Woody and I collaborated for over 30 years and published many highly cited papers together. His two most cited papers were both published in Science (1994 and 1998) and have been referred to by other authors 5,700 and 3,450 times, respectively,” said Dr. Shay, Professor of Cell Biology, who holds The Southland Financial Corporation Distinguished Chair in Geriatrics. “Woody was exceptionally good at developing new methods and coming up with insightful ideas on how to advance a project. We worked well together and complemented each other’s strengths. He will be missed by me and all his former students and postdoctoral trainees.”

Dr. Wright received the Lyndon Baines Johnson Research Award from the American Heart Association, a Research Career Development award from the National Institutes of Health, a Method to Extend Research In Time (MERIT) Award from the National Institute on Aging, an AlliedSignal Award for Research on Aging, the Hayflick Award from the American Aging Association, and an Ellison Medical Foundation Senior Scholar Award in Aging. He also served on the Scientific Advisory Board of the Buck Institute for Research on Aging.

Together with longtime collaborator Dr. Jerry Shay (right), Dr. Wright explored molecular mechanisms that regulate telomere shortening and telomerase activity.

In addition to being a distinguished researcher with UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, Dr. Wright had heroically waged a 13-year battle with multiple myeloma, a type of rare blood cancer, at the Cancer Center. In the midst of his success in illuminating the role of telomeres, Dr. Wright was diagnosed in 2006 with multiple myeloma and volunteered to take part in one of the nation’s first clinical trials of CAR-T therapy. “I don’t know if it’s because of what I went through or if it’s a normal part of aging, but I have a strong desire to give back,” he had explained in a 2018 interview.

Born June 21, 1949, Dr. Wright received his Bachelor of Arts degree, summa cum laude, from Harvard College in 1970, a Ph.D. under the direction of Dr. Leonard Hayflick in 1974, and an M.D. from Stanford University School of Medicine in 1975. He joined the UT Southwestern faculty as an Assistant Professor following a postdoctoral fellowship at the Pasteur Institute in Paris with Dr. Francois Gros. Dr. Wright became an Associate Professor in 1985 and was promoted to Professor in 1992. At UTSW, he had previously held the Southland Financial Corporation Distinguished Chair in Geriatric Research.

Dr. Wright garnered national and international attention to his work through more than 140 seminars and lectures at major universities and meetings throughout the U.S. and the world, more than 320 published articles, reviews, and book chapters, and 27 patents related to methods for the diagnosis, treatment, and analysis of telomere length, telomerase activity, and other anti-cancer therapies.

Dr. Wright also was a committed and passionate educator. He mentored more than 35 graduate students and 70 postdoctoral fellows during his long and distinguished career. His excellence in the classroom was recognized by Outstanding Teacher Awards in 1993, 1994, 1999, 2008, and 2012. More than four decades of former medical students will remember the songs he wrote and performed to explain topics he was lecturing on in medical histology.

Funeral arrangements are being made with Wade Family Funeral Home in Arlington: 4140 W. Pioneer Parkway, Arlington, TX 76013. Visitation will be held 6 to 8 p.m. Wednesday, Aug. 7. A memorial service begins at 4 p.m. Thursday, Aug. 8.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

Resources

• Radiation treatment for kidney cancer
• Video: Definitive radiation treatment for kidney cancer and metastases
• Clinical trials

DALLAS – Aug. 1, 2019 – Investigators at UT Southwestern Medical Center’s Simmons Comprehensive Cancer Center, who are members of the Kidney Cancer Program, report an innovative strategy for treating advanced kidney cancer. In a longitudinal study published today in the International Journal of Radiation Oncology, Biology, Physics, researchers show how the use of a powerful, targeted radiation technique called stereotactic ablative radiotherapy (SAbR) can effectively treat metastatic disease while delaying the need for systemic (drug) treatments, which often come with side effects.

Metastatic kidney cancer is uniquely challenging because the disease can act so differently from one patient to the next. When a tumor metastasizes and spreads to other parts of the body, it does so with varying degrees of severity. Some kidney cancer patients have oligometastatic disease, from the Greek word oligos meaning “few,” and have a small number of metastases. With a limited number of tumors, investigators discovered that it is possible to control the disease by tightly targeting the tumors with high doses of radiation that kill the cancer.

Dr. Raquibul Hannan

In the study, 47 patients received ablative radiation to a combined 68 tumors, resulting in control rates of over 90 percent two years after the radiation therapy. Most patients received one course of radiation with some receiving up to three rounds to target tumors that appeared after the initial SAbR treatment, according to Dr. Raquibul Hannan, radiation oncology co-leader of the Kidney Cancer Program and co-corresponding author of the study – along with Drs. Robert Timmerman and James Brugarolas. Remarkably, two and a half years later, nearly 40 percent of patients did not need any additional treatment beyond SAbR. While this follow-up time is relatively short, the results suggest that for some patients, radiation alone may be enough to control their disease long term. This finding could have a significant impact on patients’ quality of life, since radiation therapy was well tolerated, while systemic, or whole-body drug treatments like targeted therapy and immunotherapy often include a myriad of unpleasant and even toxic side effects.

While metastatic disease could not be ultimately controlled with local radiation alone for some patients, SAbR delayed the use of systemic therapy by 15 months, on average. Importantly, the duration and effectiveness of subsequent drug treatment was seemingly unaffected by SAbR, suggesting that SAbR may provide a survival benefit to patients and preserve their quality of life while leaving the door open for follow-up therapies, if needed.

“This is a potential paradigm shift in how we view and treat advanced disease by outright delaying the use of systemic therapy until otherwise necessary,” Dr. Hannan said.

Dr. Robert Timmerman

Dr. Timmerman, a SAbR pioneer and Fellow of the American Society for Radiation Oncology, echoed the novelty of the approach. “What is truly innovative is the use of SAbR to control the cancer not just initially, but while it remains oligometastatic,” he said. “To my knowledge, this is the first time that SAbR was used in such a manner in any cancer type.”

The study builds on a long-standing tradition of pioneering radiation therapy approaches at UT Southwestern, where the largest series of avant-garde SAbR treatment for kidney cancer was recently reported (Wang et al., 2017).

“This is an approach worth considering for selected patients,” said Dr. Brugarolas, Director of the UT Southwestern Kidney Cancer Program. “The study shows how multidisciplinary care can bring new treatment options for our patients.”

The oligometastatic treatment paradigm is being evaluated in a prospective phase two clinical trial (NCT02956798) led by Drs. Hannan and Brugarolas, which is currently accruing patients at UT Southwestern. “A national study is also under consideration,” Dr. Hannan added.

Dr. Hannan is an Associate Professor of Radiation Oncology and Immunology. Dr. Timmerman, Professor of Radiation Oncology and Neurological Surgery, holds the Effie Marie Cain Distinguished Chair in Cancer Therapy Research. Dr. Brugarolas, Professor of Internal Medicine, holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Also contributing to the study were Dr. Yuanyuan Zhang, Jonathan Schoenhals, Alana Christie, Dr. Osama Mohamad, Chiachien Wang, Dr. Isaac Bowman, Dr. Nirmish Singla, Dr. Hans Hammers, Dr. Kevin Courtney, Dr. Aditya Bagrodia, Dr. Vitaly Margulis, Dr. Neil Desai, Dr. Aurelie Garant, and Dr. Hak Choy. Dr. Hammers is a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine, and Drs. Bagrodia and Desai are both Dedman Family Scholars in Clinical Care. Dr. Choy holds The Nancy B. and Jake L Hamon Distinguished Chair in Therapeutic Oncology Research.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – July 24, 2019 – A new molecular mechanism discovered by UT Southwestern researchers indicates that drugs currently used to treat less than 10 percent of breast cancer patients could have broader effectiveness in treating all cancers where the drugs are used, including ovarian and prostate cancers. The new study also revealed a potential biomarker indicating when these drugs, called PARP inhibitors, can be unleashed in the fight against cancer.

“These findings could increase the patient population benefiting from these drugs by two, three, or four-fold. Up to 70 percent of breast cancer patients could now be good candidates,” said Dr. W. Lee Kraus, Director of the Green Center for Reproductive Biology Sciences at UT Southwestern and a member of the Harold C. Simmons Comprehensive Cancer Center. “We have found that PARP inhibitors can act by a mechanism that is different from those previously identified, which rely on BRCA-dependent DNA repair pathways.”

This research helps explain why breast cancer patients can be responsive to PARP inhibitors even if they don’t have BRCA gene mutations.

The Kraus team’s findings were published in the journal Molecular Cell on July 24.

PARP inhibitors were approved by the FDA in 2014 for the treatment of ovarian cancers containing BRCA mutations, rare genetic mutations that disable a DNA repair pathway in cancer cells. The FDA also approved PARP inhibitor for breast cancer treatment in 2018. In their current use, doctors prescribe PARP inhibitors to disable a second DNA repair pathway, making it difficult for cancer cells to survive.

Dr. Kraus’ lab discovered that while this war on DNA repair is being waged, PARP inhibitors are also battling for dominance elsewhere in the cancer cell. It is an important, effective fight previously unknown to science. The PARP inhibitors also attack the machinery that makes proteins, called ribosomes.

“Cancer cells are addicted to ribosomes. Cancer cells grow fast and must make proteins to support cell division and other essential processes going on in the cell. If you can slow down or inhibit the production of ribosomes, then you can slow down the growth of the cancer cell,” Dr. Kraus said.

This new understanding changes the way that scientists and clinicians think about PARP inhibitors and their clinical applications, which previously have been focused on DNA repair pathways since the initial discoveries in 2005. It took more than a decade to get PARP inhibitors approved by the FDA. New applications of PARP inhibitors based on Dr. Kraus’ discovery could reach patients much quicker because three PARP inhibitor drugs are already approved and in use.

“The historical view is that cancers need the mutated BRCA gene to be sensitive to PARP inhibitors. That’s what most scientists and clinicians thought,” Dr. Kraus said. “But what the field is now coming to realize is that’s just not true.”

The realizations Dr. Kraus mentioned come from recent laboratory science, preclinical studies, and clinical trials throughout the nation that show additional signs of PARP inhibitors’ effectiveness in the absence of BRCA mutations. But a clear molecular explanation for these effects has been lacking – until now. 

The new study maps out this molecular pathway in its entirety and identifies a potential biomarker, a clinical test, that might indicate which patients may benefit from PARP Inhibitors. The biomarker is based on a protein called DDX21, which is required for the production of ribosomes in small subcellular compartments called nucleoli. The presence and function of DDX21 in the nucleolus requires PARP-1, the target of PARP inhibitors. Treatment with PARP inhibitors blocks DDX21 function and causes it to leak out of the nucleolus and disburse throughout the nucleus, thus inhibiting ribosome production. High levels of DDX21 in the nucleolus indicate cancers that might be the most responsive to PARP inhibitors.

The Kraus team found the new pathway and potential biomarker by examining a wide spectrum of breast cancer cells, some of which naturally have low levels of PARP. The low-PARP-level cells behaved like cells in which PARP activity was reduced by PARP inhibitors. The discovery builds on 15 years of PARP research so intense that Dr. Kraus’ laboratory team put a molecular model of PARP-1 on his birthday cake.

“We started by trying to identify new molecular mechanisms and pursued this line of inquiry. We didn’t know where the study would lead,” he said. “We started as pure basic scientists, but as the study progressed the clinical relevance became more evident.”

The next step is clinical trials Dr. Kraus is currently developing with UT Southwestern oncologists who treat breast and ovarian cancers.

Dr. Carlos Arteaga, Director of the Simmons Comprehensive Cancer Center, asked Dr. Kraus to speak about this potential new application of PARP inhibitors at the Wendy and Emery Reves International Breast Cancer Symposium on Sept. 20 and 21.

“This is a stellar example of our commitment to translational research; Dr. Kraus sought and secured Institutional Review Board approval for clinical trials with PARP inhibitors before the article was even published. This speaks to the commitment of the Cancer Center to bringing the benefits of our basic science discoveries in cancer directly to patients,” Dr. Arteaga said.

Dr. Kraus is a founder and consultant for Ribon Therapeutics, Inc., which studies PARP inhibitors, and he holds a patent covering reagents used in this research. 

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – July 16, 2019 – Dr. Phil Evans is so deeply involved in nonprofit cancer groups that a luncheon with the National Breast Cancer Foundation was a routine item on his calendar. But the event turned out to be anything but ordinary. Dr. Evans was stunned with a Lifetime Achievement Award.

“I was just floored. I couldn’t believe it. It was just such a surprise,” said Dr. Evans, a Professor of Radiology who serves as Chief of the Breast Imaging Division.

The Frisco-based breast cancer charity honored him in May for his decades of work with and on behalf of breast cancer patients, including his recent efforts to help raise $40 million for a new breast center at Parkland Memorial Hospital. Scheduled to open in 2021, the center will more than double the number of breast cancer patients visits from 40,000 to 100,000.

National Breast Cancer Foundation founder and CEO Janelle Hail said Dr. Evans’ work on the fundraising campaign coupled with his reputation as a compassionate and attentive doctor made him ideal for the award.

“For 40-plus years, Dr. Evans has devoted his career to improving the health of women. As a diagnostic radiologist, he has fought tirelessly to screen and diagnose women early while serving on the medical staff and also as a leader at one of our most prestigious partner hospitals, Parkland,” she said.

The National Breast Cancer Foundation is just one of many organizations that Dr. Evans has worked with to advance cancer care. He served as President of the Society of Breast Imaging and of the American Cancer Society. He also joined several committees of Susan G. Komen, the prominent breast cancer foundation based in Dallas.

“That’s the way you get things done,” he said.

When Dr. Evans talks about the nonprofit groups, he quickly gets into the details of their organizational structure, history and goals. It’s a testament to how heavily involved he is. He cites nonprofit work and patient groups as medicine’s major partners in cutting the breast cancer mortality rate in recent decades. Breast cancer deaths dropped 39 percent from 1989 to 2015, according to the American Cancer Society.

His affable demeanor, well known among the nonprofit groups, extends into patient care.

Frisco resident Linda Neal, a patient of his for more than two decades, said she trusted him so much she followed him from one hospital to the next and later had her own daughter become one of his patients.

“I just have absolute trust in him and his knowledge,” she said explaining that patients appreciate his warm smile and calming voice. “His bedside manner is probably the best I’ve ever had in any physician – ever.”

Dr. Evans also works closely with other physicians and within institutions to advance breast cancer care. In 2013, D Magazine named him one of “The Dallas Dozen,” the magazine’s annual list of 12 influential people in Dallas. The magazine described that year’s distinguished group as people who “would rather be in the trenches getting things done.”

Dr. Evans currently serves on the Planning Committee for the Wendy and Emery Reves International Breast Cancer Symposium. The premier event, hosted by UT Southwestern Simmons Cancer Center, will spotlight the most recent progress in breast cancer research and clinical care. Dr. Evans recruited two speakers for the September symposium: Dr. Debra Monticciolo, President of the American College of Radiology, and Dr. Robert Nishikawa, an artificial intelligence expert at the University of Pittsburgh.

“It’s a world-class group of people coming for this symposium,” Dr. Evans said. “It’s the real cutting-edge people in breast cancer.”

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

The authors of the study published this month in the Journal of Clinical Oncology investigated why many cancer clinical trials fail to enroll enough patients. The researchers sought to identify potential interventions – i.e., solutions – to improve the situation.

Research in the Department of Population and Data Sciences investigates ways to improve health care delivery on a population level. Its studies often involve breaking a problem into its component steps, identifying potential barriers at each step, and developing a list of possible interventions for future study. In this specific project, the researchers approached suboptimal clinical trial enrollment – a significant national concern – as a health care delivery issue.

Dr. Celette Sugg Skinner

“Cancer clinical trials are meant to result in treatment advances. However, their potential benefits are diminished by suboptimal trial participation, both by patients and by clinicians and their organizations,” said Dr. Celette Sugg Skinner, Chair and Professor of Population and Data Sciences and corresponding author of the study. Dr. Skinner is also a member of the Harold C. Simmons Comprehensive Cancer Center and holds the Parkland Community Medicine Professorship.

Nearly half – 40 percent – of cancer trials fail to reach targets for accrual, the medical term for the number of patients who have completed or will complete the trial. Fewer than 2 percent of adults with cancer enroll in trials, and last year no trials were offered in 36 percent of physician-owned and 14 percent of hospital-owned oncology practices, she said.

In order to help ensure results will reach statistical significance, clinical trials are designed to enroll a calculated number of patients, she explained. “Before we can figure out how to improve accrual in trials, we need to better understand the entire process and challenges along the way.”

Dr. Simon Craddock Lee

To gain this understanding, lead author Dr. Simon Craddock Lee, Associate Professor in the Department, conducted in-depth interviews with 10 key oncology physicians, nurses, and research staff in leadership positions across nine states.

“Nationally, we know there are large numbers of cancer patients and relatively few of them are in clinical trials,” Dr. Lee said. “Most of the research to date has focused on the idea that the problem must be that patients don’t know about clinical trials.”

That mindset led to a research emphasis on improving communication so that patients are aware of trials and understand the risks and benefits as well as reaching out to underrepresented populations and ensuring messages are culturally appropriate – all worthy goals. However, this study identifies another group of problems, he explained.

The researchers found that emerging therapies and the changing landscape of oncology have introduced complexity, he continued. Specifically, oncology practices encounter barriers to (1) staying aware of available trials, (2) identifying eligible patients, (3) introducing the idea of trial participation vs. standard treatment to those patients, and (4) enrolling and caring for them throughout clinical trials.

These steps have become more complicated due to emerging discoveries in the realm of precision oncology, which seeks to determine the best treatment based on patient genetic, environmental, or lifestyle factors. For example, whereas trials in the past would enroll all patients with stage 2 breast cancer, current trials often are designed to enroll only patients with certain biomarkers.

“As eligibility criteria become more numerous and specific, the likelihood of any patient meeting all criteria goes down,” Dr. Lee explained. “Because oncology practices are not reimbursed for determining and documenting enrollment, trial accrual is threatened as these tasks become more costly and time-consuming.”

The authors suggest that addressing challenges to trial accrual may involve changes in trial-specific reimbursement, as well as incentives for administrative and infrastructure costs.

Dr. David Gerber

“Our next goal must be to enhance logistic, infrastructure, and policy support to translate oncology discoveries into high-quality cancer care,” said co-author Dr. David Gerber, a Professor of Internal Medicine and Population and Data Sciences. Dr. Gerber serves as Associate Director for Clinical Research and co-Leader of the Experimental Therapeutics Program in the Simmons Cancer Center.

The researchers will use this study to guide future investigations. Most immediately, they have surveyed more than 1,000 oncology providers, asking in-depth questions about the barriers identified in this study. Findings from that survey will help to identify strategies to ensure that clinical trials enroll the targeted number of patients.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – June 3, 2019 – A novel imaging test shows promise for identifying kidney cancer patients most likely to benefit from immunotherapy.

In a study published today in the Journal for ImmunoTherapy of Cancer, investigators with the UT Southwestern Medical Center Kidney Cancer Program developed a new test to illuminate kidney cancers that may respond to checkpoint inhibitors.

The strategy involved transforming an immunotherapy drug, atezolizumab (Tecentriq, Genentech/Roche Group), into a diagnostic tracer. Atezolizumab, which is used to treat lung, breast, and bladder cancer, binds to and disables PD-L1, a protein that cancer cells display on their surface to shut off approaching killer immune cells. By labeling atezolizumab with zirconium-89 (Zr⁸⁹), a radioactive metal generated using a cyclotron, the investigators were able to visualize atezolizumab using PET (positron emission tomography). As such, a single, very small dose of Zr⁸⁹-atezolizumab can be used to evaluate whether tumors deploy PD-L1 to suppress immune cells and whether drugs disabling this pathway may be effective.

(l-r): Drs. Xiankai Sun, James Brugarolas, and Alex Bowman with UT Southwestern Medical Center have pioneered a novel imaging test to identify kidney cancer patients most likely to respond to immunotherapy.

Currently, immunotherapy drugs benefit less than 50 percent of kidney cancer patients. With immuno-PET, or iPET, as a screening tool, the investigators hope to identify those patients who will benefit. Marking the first time this type of theranostic (drug turned into a diagnostic test) is deployed for kidney cancer, the approach opens a molecular window to what is going on inside a cancer patient.

In proof-of-principle experiments, a team led by Dr. James Brugarolas, one of the corresponding authors of the study and the Director of the UT Southwestern Kidney Cancer Program, showed that Zr⁸⁹-atezolizumab was able to illuminate kidney tumors with high levels of PD-L1. As part of the study, investigators selected tumors from two patients, one with high PD-L1 and another with low PD-L1, and transplanted them into mice. The mice were then injected with Zr⁸⁹-atezolizumab intravenously and evaluated by PET. As predicted from the mouse studies, the patient with the high PD-L1 tumor had substantial regression of his metastases when treated with nivolumab (Opdivo, Bristol-Myers Squibb), which targets the PD-L1 pathway.

"The development of tests predicting which patients respond to immunotherapy is critical,” said Dr. Hans Hammers, an immunotherapy expert with the Kidney Cancer Program.

Zr⁸⁹-atezolizumab was filed with the U.S. Food and Drug Administration by the Cyclotron and Radiochemistry Program led by Dr. Xiankai Sun at UT Southwestern, also a corresponding author of the study, and is now proceeding to evaluation in patients in a clinical trial at UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center.

The clinical trial is made possible through a $600,000 translational award to Dr. Brugarolas’ team by the V Foundation for Cancer Research. Support for the preclinical studies was provided through a Specialized Program of Research Excellence (SPORE) grant from the National Cancer Institute.

“We are hopeful that iPET will identify kidney cancer patients most likely to benefit from checkpoint inhibitors,” said Dr. Alex Bowman, Principal Investigator in the clinical trial, along with Dr. Brugarolas and Dr. Orhan Öz.

A second trial also is planned at the Simmons Cancer Center using Zr⁸⁹-atezolizumab to evaluate the impact of stereotactic body radiation therapy (SBRT) on PD-L1 expression in kidney cancer patients.

“SBRT has the potential to induce inflammation and activate an immune response, and we are excited to evaluate this therapy further in patients using iPET,” said Dr. Raquibul Hannan, a leader in radiation therapy for kidney cancer and Principal Investigator of the study. The SBRT trial will be funded by the Kidney Cancer Congressionally Directed Medical Research Program.

Dr. Brugarolas, a Professor of Internal Medicine, holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Dr. Hammers is an Associate Professor of Internal Medicine and a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine. Dr. Sun, an Associate Professor of Radiology and in the Advanced Imaging Research Center, holds the Dr. Jack Krohmer Professorship in Radiation Physics. Dr. Öz, a Professor of Radiology, holds The Wechun Pak Professorship of Bone Biophysics. Dr. Hannan is an Associate Professor of Radiation Oncology and Immunology. Dr. Bowman is an Assistant Professor of Internal Medicine. Also contributing to the study were Dr. Joseph Vento; Dr. Aditi Mulgaonkar; Layton Woolford; Kien Nham; Alana Christie; Dr. Aditya Bagrodia; Dr. Alberto Diaz de Leon; Dr. Renee McKay; Dr. Payal Kapur; Dr. Guiyang Hao; and Dr. Marianna Dakanali.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – May 23, 2019 – E-cigarette use is climbing among cancer patients and cancer survivors, according to a new study by a UT Southwestern Medical Center oncologist.

Dr. Nina Sanford’s study found that:

• E-cigarette use among people with a cancer diagnosis increased from 8.5 percent in 2014 to 10.7 percent in 2017.
• The increase happened even as conventional smoking remained stable.
• E-cigarette use is especially high among young cancer patients (under the age of 50). More than a quarter of them use e-cigarettes, and it keeps going up: 23 percent of cancer patients under 50 reported using e-cigarettes in 2014 compared with 27 percent in 2017.

“The gradual but steady increase is quite striking,” said Dr. Sanford an Assistant Professor of Radiation Oncology and doctor who specializes in treating cancers of the gastrointestinal tract. “The high prevalence of e-cigarette use among younger cancer patients and survivors is concerning.”

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Dr. Sanford’s analysis was based on data from the Centers for Disease Control and Prevention’s National Health Interview Survey, which included more than 13,000 cancer patients from 2014 to 2017. Her findings were published in the journal JAMA Oncology in February.

The study findings shed new light on e-cigarette use as the products gain increased attention ranging from federal government crackdowns on e-cigarette sales to claims that e-cigarettes can be used to quit traditional smoking.

Usage of e-cigarettes, also called “vaping,” has medical experts concerned because of the addictive nicotine and potentially harmful toxins they deliver. The battery-operated products produce an aerosol that users inhale into their lungs like traditional smoking.

Dr. Sanford said she seized on the opportunity to study the data because there is so little known about e-cigarette use in cancer patients.

“Because e-cigarettes are relatively new, we don’t have the long-term data on their side effects yet,” she said.

With so little known about e-cigarettes and what they do to the body, Dr. Sanford said the best bet is to avoid them all together. She noted that e-cigarettes often produce harmful chemicals such as lead, nickel, and acetaldehyde. Conventional smoking can impede healing from surgery and radiation therapy so it is possible that e-cigarettes could cause similar difficulties, she said.

Dr. Sanford said patients often ask about e-cigarettes, and she recommends staying away from all kinds of smoking instead of trying to substitute e-cigarettes for traditional cigarettes.

“I don’t encourage it, but I also am honest that the jury is still out on what the long-term effects of e-cigarette use are,” she said. “These are not an FDA-regulated product. There’s wide variation of what goes into them. When you pick up an e-cig in the store, you really don’t know what’s in it.”

Regulation of e-cigarettes has just begun and so have studies of the products. Dr. Sanford said medical experts need to know much more, and it will take decades to know if e-cigarettes cause cancer.

“It’s a new area, and there’s just no long-term data on e-cig use so there’s going to be a lot of controversy on what to do until more rigorous studies are published, particularly given the diverse entities involved, ranging from cancer organizations to e-cigarette companies,” she said.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – April 11, 2019 – A stunning one-third of people with a cancer diagnosis use complementary and alternative medicines such as meditation, yoga, acupuncture, herbal medicine, and supplements.

UT Southwestern Medical Center’s Dr. Nina Sanford made the findings that’s now drawing renewed attention to habits she said cancer patients must disclose during treatment. Dr. Sanford is an Assistant Professor of Radiation Oncology who specializes in and treats cancers of the gastrointestinal tract.

Herbal supplements were the most common alternative medicine and chiropractic, or osteopathic manipulation, was the second most common, according to Dr. Sanford’s analysis of data from the Centers for Disease Control and Prevention’s National Health Interview Survey. Her findings were published in the journal JAMA Oncology.

“Younger patients are more likely to use complementary and alternative medicines and women were more likely to, but I would have thought more people would tell their doctors,” Dr. Sanford said, referring to the finding that 29 percent of people who use complementary and alternative medicine did not tell their physicians. Many survey respondents said they did not say anything because their doctors did not ask, or they did not think their doctors needed to know.

Dr. Sanford and other cancer specialists agree this is concerning, especially in the case of herbal supplements.

“You don’t know what’s in them,” Dr. Sanford said. “Some of these supplements are kind of a mishmash of different things. Unless we know what’s in them, I would recommend patients avoid using them during radiation because there’s likely not data on certain supplements, which could interfere with treatment. With radiation specifically, there is concern that very high levels of antioxidants could make radiation less effective.”

Dr. David Gerber, a lung cancer specialist and a Professor of Internal Medicine and Population and Data Sciences at UTSW, said physicians need to know if their patients use herbal supplements because they can completely throw off traditional cancer treatments.

“They may interact with the medicines we’re giving them, and through that interaction it could alter the level of the medicine in the patient,” he said. “If the levels get too high, then toxicities increase, and if the levels get too low, the efficacy would drop.”

Nancy Myers wanted to use supplements during her 2015-2017 cancer treatments, but she ran it by her doctors first.

“I would ask the physician, ‘Could I?’ and everyone said, ‘No, we don’t know how that interacts with your conventional medicine,’ so I respected that,” the 47-year-old mother of four said. Only after treatment did she start taking turmeric, omega-3, vitamin D, and vitamin B6.

“I have plenty of friends in this cancer journey who I’ve met who take supplements. A lady I met recently takes 75 supplements a day. It takes her two hours to package her supplements every week,” she said.

Ms. Myers said every person in her cancer support group uses some kind of alternative medicine. In addition to supplements, she practices meditation and yoga with guidance from a smartphone app.

“It’s what we can control. We can’t control the whole cancer,” she said. “It helps because it takes your mind off just thinking about it.”

Dr. Nina Sanford

She said she knows of some people with cancer who use only alternative medicine – and no traditional medical treatments. Dr. Sanford said this is a dangerous approach that could be fatal. The most famous case of this was Apple founder Steve Jobs, who reportedly used special diets, acupuncture, and other alternatives after receiving a diagnosis of pancreatic cancer. He turned to traditional medicine late in his battle with cancer and died in 2011.

While doctors are highly cautious about the use of herbs and other supplements during treatment, they are much more open to meditation and yoga as practices that can help patients cope with the shock of a cancer diagnosis and the stress of chemotherapy, radiation, and surgery.

“We strongly advise patients to stay active and engage in exercise during treatment,” Dr. Sanford said. “A common side effect of radiation is fatigue. I let the patients know that the patients who feel the most fatigue are the ones who are the most sedentary and that those who are doing exercise are the ones who frequently have the most energy.”

Belindy Sarembock, 53, of Dallas, said she practiced yoga during her treatments for breast cancer. She started the classes with skepticism and quickly became convinced of the benefits.

“I was one who would have laughed at yoga before breast cancer, but now it just helps me so much,” she said. “It’s just so relaxing, I just feel so good after I leave. It’s just so peaceful. For your body, I can’t think of anything better than that.”

She said she had neuropathy or nerve damage from chemotherapy, and yoga almost immediately took the pain away.

“I couldn’t get onto my toes. After the second time of going to yoga, I was able to go onto my toes,” she said. “I wish I would have known about the yoga earlier. It was just such a benefit and helped me so much. I highly recommend it to anyone.”

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – April 9, 2019 – UT Southwestern Medical Center now offers more precise radiation treatments for breast cancer with a new, cutting-edge device that is only the second of its kind in the world.

The GammaPod delivers higher doses of radiation to a narrowly targeted area, meaning breast cancer patients will have fewer treatments over shorter periods of time.

“It’s going to be a great service to the community and offer a lot to women who are facing breast cancer with the busy lives that they have today,” said Dr. Asal Rahimi, an Associate Professor of Radiation Oncology, Director of Clinical Research, and a breast cancer expert. “Our mission is to try to provide very effective treatment in as little time as possible.”

Dr. Asal Rahimi standing with the GammaPod

The GammaPod breaks new ground with vacuum suction that temporarily immobilizes the breast, holding it perfectly still so radiation hits its target and spares healthy tissue. The suction pulls the breast up against the wall of a fitted plastic cup, much like a breast pump for breastfeeding. The sensation is nearly the same.

Before stereotactic radiation is delivered, a CT scan pinpoints the tumor’s exact location within the breast held by suction.

With the location positively identified and entered into a computer, the patient then presses up against the GammaPod’s large vertical, rectangular table. There is a hole where the breast cup slides through. The foam padded table tilts 90 degrees to a horizontal position, so the patient is lying face down for treatment. The breast is downward, thereby eliminating radiation near the heart or lungs.

The GammaPod’s unique configurations allow oncologists to narrow radiation down to a range of just 3 millimeters, or less than that of three stacked pennies. Standard radiation treatment for breast cancer patients typically lasts four to six weeks, but with the stereotactic radiation delivered by the GammaPod, treatment can be shortened to just one to five days and potentially lower the toxicity of treatment.

One of UT Southwestern’s first GammaPod patients, Patricia Salcido, 60, of Grand Prairie, said she was a bit nervous before her first treatment and completely at ease after it.

“I feel that I could feel it inside working. The new technology is wonderful. I totally believe in it,” Ms. Salcido said, as she faced the GammaPod, waiting for her third treatment. “I fly up there, lie on my cheek and just let the machine do the work, and the results will come later.”

She said the most memorable sensation is pressure on her cheek as she lies with her face turned to the side. There is no pain.

Ms. Salcido is a typical GammaPod patient, requiring five roughly 20-minute treatments.

Dr. Rahimi said possible side effects could be minor blistering and bruising. Ms. Salcido said she’s not had any of that.

“I have had no side effects. None! I sleep like a baby,” she said smiling.

Dr. Rahimi co-chairs the GammaPod Consortium with a doctor from the University of Maryland, where the GammaPod was initially developed. She said clinical trials are ongoing and more are planned. Doctors will likely mix the GammaPod’s advantages with other resources in Radiation Oncology to personalize treatment to the size of patients’ breasts and tumors.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

DALLAS – March 13, 2019 – The Cancer Prevention and Research Institute of Texas (CPRIT) has awarded UT Southwestern Medical Center faculty more than $18.4 million for cancer research and faculty recruitment.

The state funding will advance scientific understanding of breast, lung, prostate, and other types of cancer.

“We are enormously grateful for the support from CPRIT, which is essential for our mission to prevent cancer and treat patients with cancer in our catchment area in North Texas, as well as recruit some of the best talent in the country to UT Southwestern,” said Dr. Carlos L. Arteaga, Director of the Harold C. Simmons Comprehensive Cancer Center and holder of The Lisa K. Simmons Distinguished Chair in Comprehensive Oncology.

UT Southwestern leaders will use $8 million to recruit new faculty, while $10 million will help UTSW researchers study cancer on the cellular, molecular, and genetic levels.

The amounts and focuses of the new CPRIT grants include:

• $1.2 million to help Dr. Jacques Lux develop nanoparticles that encapsulate asparaginase, an enzyme that degrades asparagine, causing leukemia cancer cells to die without harming normal cells. His work is critical because although asparaginase is nearly universally used in the treatment of acute lymphoblastic leukemia, it is highly allergenic in 30 percent of children. If successful, this new platform would prolong the functional life of the enzyme in the bloodstream while effectively hiding it from the child’s immune system to prevent allergic reactions. Dr. Lux is an Assistant Professor of Radiology.
• $1,189,577 million to assist Dr. Ananth Madhuranthakam with clinical translation and evaluation of a novel whole-body imaging technique developed for improved detection and response assessment in multiple myeloma patients. If successful, this approach will provide timely management of cancer that can occur anywhere in the body and cause painful bone lesions. The new technique will also eliminate patients’ exposure to radiation and significantly reduce scan times. Dr. Madhuranthakam is an Assistant Professor of Radiology and in the Advanced Imaging Research Center.
• $900,000 to help Dr. Hesham Sadek and Dr. Asaithamby Aroumougame study chest radiation and chemotherapy’s harmful effects on the heart. These treatments in young cancer patients substantially increase the risk of developing heart failure. Heart cells divide more slowly than other cells so the effects of cancer treatments on the heart are not well understood. Dr. Sadek, an Associate Professor of Internal Medicine and Molecular Biology, holds the J. Fred Schoellkopf, Jr. Chair in Cardiology. Dr. Aroumougame is an Assistant Professor of Radiation Oncology.
• $900,000 to help Dr. Jian Xu understand how acquired mutations in noncoding DNA sequences, which control when genes are turned on and off, can lead to acute myeloid leukemia. This research is a necessary step to uncover how leukemia develops and to find new treatments. Dr. Xu is an Assistant Professor at the Children’s Medical Center Research Institute at UT Southwestern and of Pediatrics.
• $900,000 to help Dr. Ram Mani’s lab construct three-dimensional maps of a protein that mediates looping interactions that genes use to interact with regulatory DNA elements. These looping interactions are often hijacked by cancer. Dr. Mani will study this process in prostate cancer. He is an Assistant Professor of Pathology and Urology.
• $899,747 to help Dr. W. Lee Kraus tackle a new and uncharacterized class of RNA molecules that appears to play a role in the development of breast cancer. These molecules code for a short polypeptide involved in every important step in breast cancer: proliferation, tumor formation, migration, invasion and metastasis.
• An additional $899,397 for Dr. Kraus’ lab to study the interplay between the estrogen receptor, a protein involved in the hormone-dependent growth of many breast cancers, and PARP-1, a protein that serves as the target of novel PARP inhibitor drugs recently approved by the Food and Drug Administration. His lab will focus on the molecular mechanisms through which these two proteins control gene expression. Dr. Kraus, a Professor of Obstetrics and Gynecology and Pharmacology, holds the Cecil H. and Ida Green Distinguished Chair in Reproductive Biology Sciences.
• $896,892 to help Dr. Gary Hon’s lab perform analyses on the cellular and molecular functions of changes in DNA sequences related to breast cancer. The study will look at enhancers, genes, and pathways contributing to breast cancer, and it could lead to earlier breast cancer detection. Dr. Hon is an Assistant Professor of Obstetrics and Gynecology and Bioinformatics.
• $881,433 to assist Dr. Diego Castrillon’s study of the most aggressive form of endometrial cancer, also known as uterine cancer. He will focus on a change in a gene that leads to the formation of cancer of the uterus. Dr. Castrillon, a Professor of Pathology, holds the Vernie A. Stembridge, M.D., Distinguished Chair in Pathology.
• $885,185 to help Dr. Guanghua Xiao develop artificial intelligence models to correlate tumor tissue images from lung cancer patients with molecular profiling data. This approach will give doctors a much sharper picture of the patient’s cancer and a computer model that they can use to test therapies. Dr. Xiao is an Associate Professor of Population and Data Sciences and Bioinformatics.
• $864,000 to help Dr. Cheng-Ming Chiang’s lab investigate the role of a new class of compounds targeting breast cancer-associated gene expression and their selectivity between cancer and normal cells. Dr. Chiang is a Professor in the Simmons Cancer Center and of Pharmacology.

About the Harold C. Simmons Comprehensive Cancer Center

UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center, the only NCI-designated Comprehensive Cancer Center in North Texas, includes 12 major cancer care programs with a focus on treating the whole patient with innovative therapies, while fostering groundbreaking basic and translational research that can improve patient care and prevent cancer worldwide. In addition, the Center’s education and training programs support and develop the next generation of cancer researchers and clinicians. The Simmons Cancer Center is among only 30 U.S. cancer research centers to be named a National Clinical Trials Network Lead Academic Participating Site, a prestigious designation by the NCI, and the only cancer center in North Texas to be so designated. The designation and associated funding is designed to bolster the cancer center’s clinical cancer research for adults and to provide patients access to cancer research trials sponsored by the NCI, where promising new drugs often are tested.

About Children’s Medical Center Research Institute

Children’s Medical Center Research Institute at UT Southwestern (CRI) is a joint venture of UT Southwestern Medical Center and Children’s Medical Center Dallas, the flagship hospital of Children’s Health. CRI’s mission is to perform transformative biomedical research to better understand the biological basis of disease. Located in Dallas, Texas, CRI is home to interdisciplinary groups of scientists and physicians pursuing research at the interface of regenerative medicine, cancer biology, and metabolism. For more information, visit: cri.utsw.edu. To support CRI, visit: cri.utsw.edu/support/.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,500 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 3 million outpatient visits a year.

Update: Video added on January 24, 2019

DALLAS – April 3, 2018 – A one-two combo punch using two currently available drugs could be an effective treatment for the majority of lung cancers, a study by scientists with UT Southwestern’s Simmons Cancer Center shows.

Dr. Amyn Habib is Associate Professor of Neurology and Neurotherapeutics with the Simmons Cancer Center and the O’Donnell Brain Institute at UT Southwestern.

Researchers found that a combination of drugs – one targeting epidermal growth factor receptor (EGFR) and one targeting tumor necrosis factor (TNF) – effectively blocks the cancer from using TNF as an escape route. Using a mouse model, the researchers showed that when TNF is also blocked, the cancer becomes sensitive to EGFR treatment.

“There has been a tremendous effort over the past several years to block EGFR as a treatment for lung cancer, but this therapy only works in a small subset of patients. The cancer fights back with a bypass pathway,” said senior author Dr. Amyn Habib with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern and a staff physician at the Dallas Veterans Affairs Medical Center.

“Blocking both of these proteins could be a treatment that is beneficial for the majority of lung cancer patients,” said Dr. Habib, Associate Professor of Neurology and Neurotherapeutics with UT Southwestern’s Peter O’Donnell Jr. Brain Institute.

Lung cancer is the most common cause of cancer deaths in the U.S. for both men and women, according to the National Cancer Institute and in 2017, lung cancer caused 26 percent of all cancer deaths. Non-small cell lung cancer (NSCLC), the type of lung cancer for which the EGFR/TNF inhibitor combination would be effective, comprises approximately 85 percent of all lung cancers.

Building on success

The latest findings build on previous work by Dr. Habib’s lab showing that the same combination of drugs was successful in a mouse model of glioblastoma, a deadly type of brain cancer.

Researchers are now planning a phase 2 clinical trial of the two-drug strategy, and because the two drugs are already FDA-approved, they hope to be able to launch the trial within a year, said oncologist Dr. David Gerber with the Simmons Cancer Center, who will lead the trial.

The clinical trial being planned will test the treatment in both lung cancer patients and those with glioblastomas.

“If this strategy is effective, then it might be broadly applicable not only against lung cancer but also against other cancers that express EGFR, which include brain, colon, and head and neck cancers,” said Dr. Gerber, Associate Professor of Internal Medicine and Clinical Sciences.

Another advantage of the anti-EGFR/TNF strategy is that the drugs are well-tolerated. Both the EGFR inhibitors and TNF inhibitors fall into the category of targeted drugs, meaning they affect specific molecules within cancer cells, and therefore have fewer side effects. Traditional chemotherapy drugs, on the other hand, have broad effects, killing cells in both cancer and healthy tissue, and leading to many unpleasant side effects.

Until now, EGFR inhibitors have only been effective at treating the 10 to 15 percent of non-small cell lung cancers that have a variant of EGFR, but the two-drug combo could potentially work for all non-small cell lung cancers, explained Dr. John Minna, Director of the Hamon Center for Therapeutic Oncology Research and Professor of Internal Medicine and Pharmacology.

“This finding has the possibility of dramatically altering how we treat lung cancer,” said Dr. John Minna, who holds the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research and the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology at UT Southwestern, which is recognizing its 75^th-year anniversary in 2018.

A new study demonstrated that using two currently available drugs could be an effective treatment for the majority of lung cancers. The bottom row shows tumors treated with the drug combo, compared with tumors without treatment or with single treatments in the rows above.

The research appears in the Journal of Clinical Investigation. Other UT Southwestern faculty members who contributed to this research are: Dr. Boning Gao, Assistant Professor with the Hamon Center for Therapeutic Oncology Research and Pharmacology; Dr. Kimmo Hatanpaa, Associate Professor of Pathology; Dr. Kemp Kernstine, Professor of Cardiovascular and Thoracic Surgery and holder of the Robert Tucker Hayes Foundation Distinguished Chair in Cardiothoracic Surgery; Dr. Yang Xie, Associate Professor of Clinical Sciences and Bioinformatics; Dr. Hong Zhu, Assistant Professor of Clinical Sciences and with the Simmons Cancer Center; Dr. Farjana Fattah, Assistant Professor with the Simmons Cancer Center and Pathology; Dr. Masaya Takahashi, Associate Professor with the Advanced Imaging Research and Radiology; Dr. Bipasha Mukherjee, Assistant Professor of Radiation Oncology; Dr. Sandeep Burma, Associate Professor of Radiation Oncology; and Dr. Jonathan Dowell, Professor of Internal Medicine;

This work was supported in part by grants from the National Institutes of Health and by the Office of Medical Research at the Department of Veterans Affairs. It was also supported by an NCI Lung Cancer SPORE, the Cancer Prevention and Research Institute of Texas, and the Dallas VA Research Corporation.

The Harold C. Simmons Comprehensive Cancer Center, one of 49 NCI-designated Comprehensive Cancer Centers in the U.S. and the only one in North Texas, is among just 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.

DALLAS – Jan. 18, 2019 – A large, multi-center study refutes earlier suggestions that antiviral drugs for treating hepatitis C may lead to a higher recurrence of liver cancer.

Researchers at UT Southwestern Medical Center studied the records of patients who had been successfully treated for liver cancer at 31 medical centers in North America, comparing those who were and were not given direct-acting antivirals for hepatitis C. The study found no significant difference in the recurrence of liver cancer between the two groups.

Similarly, the study found no difference in the aggressiveness of the cancer in those patients who did experience a recurrence.

“Our study was inspired by a single-center study from Spanish investigators in 2016. That study gained a lot of press and sparked fear about treating liver cancer patients for their hepatitis C,” said Dr. Amit Singal, Associate Professor of Internal Medicine and Medical Director of the Liver Tumor Program. “Based on these new data, providers can feel reassured that it is safe to treat hepatitis C in these patients and allow them to receive the known benefits of hepatitis C therapy.”

Some 3.2 million individuals in the U.S., the large majority of them baby boomers, have chronic hepatitis C infection. Many of these individuals struggle with inflammation of the liver and impaired liver function, as well as cirrhosis, or scarring of liver tissue. Since 2013, effective antiviral drugs have been available to treat hepatitis C infection.

Chronic hepatitis C infection is also one of the leading causes of liver cancer. According to the Centers for Disease Control and Prevention, half of all individuals with liver cancer have underlying chronic hepatitis C infection. 

The rate of new cases of liver cancer has been rising steadily in recent decades, and the state of Texas has one of the highest rates of occurrence in the country.

When liver cancer is diagnosed early, it can be effectively treated with surgery, ablation, or radiation therapy. Sometimes liver cancer patients have their tumor successfully removed, but the underlying chronic hepatitis C infection remains and continues to impair liver function further.

In this study, published in the journal Gastroenterology, 42 percent of liver cancer survivors who were treated with direct-acting antivirals (DAAs) experienced a recurrence of their cancer, compared with 59 percent of patients who were not treated with antivirals.

“Our results suggest that use of DAA therapies is safe and potentially beneficial in hepatitis C-infected patients with a history of liver cancer,” said Dr. Singal, who holds the David Bruton, Jr. Professorship in Clinical Cancer Research and is Clinical Chief of Hepatology.

Other UT Southwestern faculty members who contributed to the study are Dr. Nicole E. Rich, Assistant Professor of Internal Medicine, and Dr. Caitlin Murphy, Assistant Professor of Clinical Sciences.

Dr. Singal is a member of the Harold C. Simmons Comprehensive Cancer Center. The Simmons Cancer Center, is one of 49 NCI-designated Comprehensive Cancer Centers in the U.S. and the only so-designated center in North Texas.

Funding for this study was provided by the National Cancer Institute and AbbVie Inc. Dr. Singal has served on advisory boards and has received funding from Gilead and AbbVie. He has previously participated in a speakers’ bureau for Gilead. Other disclosures unrelated to this research appear in Gastroenterology.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 2.4 million outpatient visits a year.

DALLAS – Jan. 15, 2019 – If you’ve vowed to improve your family’s health in 2019, here’s a simple equation to memorize: cervical cancer = HPV.

Almost all cases of cervical cancer are caused by human papillomavirus, or HPV, making it a preventable cancer, say UT Southwestern Medical Center physicians.

All preteens should get the HPV vaccine at age 11 or 12, according to Centers for Disease Control and Prevention recommendations. If the preteen immunization was missed for some reason, women can still get the HPV vaccine up to age 26 and men can get it up to age 21.

The HPV vaccine is a series of shots given over several months.

Dr. David Miller, Professor of Obstetrics and Gynecology at UT Southwestern

“More than 13,000 women are expected to develop cervical cancer in the U.S. this year, but screening can catch it early enough for it to be successfully treated,” says Dr. David Miller, Professor of Obstetrics and Gynecology at UT Southwestern.

Current U.S. Preventive Services Task Force (USPSTF) screening recommendations recognize the fundamental role of HPV in causing cervical cancer and offer HPV testing as a screening option. The USPSTF recommends a Pap smear every three years for women 21 to 65 years old or, for women 30 to 65, HPV testing every five years.

“Cervical cancer deaths have fallen dramatically in recent decades, but we need to do even better. Nobody should die of cervical cancer in the U.S.,” says Dr. Miller. “It’s a slow-growing cancer and can be treated if it is caught early by appropriate screening.”

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 2.4 million outpatient visits a year.

DALLAS – Oct. 23, 2018 – UT Southwestern scientists, working with colleagues at a sister institution in Houston, have identified a new target for battling a deadly form of leukemia.

The findings raise the possibility of a novel treatment for this subtype of blood and bone marrow cancer – known as acute myeloid leukemia or AML – by attacking a harmful molecule found on the cancerous cells and also reactivating the body’s white blood cells to fight them.

The study, published in Nature, found that the molecule leukocyte immunoglobulin-like receptor B4, or LILRB4, can turn off white blood cells that normally fight AML. The molecule also helps the cancer spread to internal organs such as bone marrow, the liver, and the brain.

“AML is a terrible disease. The five-year survival rate is 27 percent in the U.S., even after treatment,” said Dr. Chengcheng “Alec” Zhang, senior author of the study and Professor of Physiology at UT Southwestern. “We identified a new target for treatment of some types of AML.”

Each year in the U.S., about 20,000 new cases of AML are diagnosed and more than 10,000 people die of the disease, according to the National Cancer Institute. The subtypes of AML involved in this study are those known as “monocytic” leukemia cells.

UT Southwestern researchers zeroed in on LILRB4 in 2013 because of early evidence that it was the culprit turning off the body’s immune response against monocytic AML. First, they uncovered the mechanism the molecule uses to do that, Dr. Zhang said, and then they began looking for an antibody that could disarm LILRB4 by blocking its signaling to turn off the white blood cells.

Dr. Chengcheng “Alec” Zhang

The following year, UT Southwestern teamed up with The University of Texas Health Science Center at Houston (UTHealth) to collaborate with researchers respected for work with antibodies, Drs. Zhiqiang An and Ningyan Zhang, who had previously worked in the biotechnology and pharmaceutical industry.

Together, the two institutions developed an antibody that can inhibit LILRB4 in mouse models injected with human leukemia cells. The UT System has exclusively licensed the related patent applications to California-based Immune-Onc Therapeutics Inc., which contributed to the research and is conducting preclinical studies.

If those studies go well, an application to the Food and Drug Administration to begin human clinical trials could come as early as next year, said Dr. Zhang, who holds the Hortense L. and Morton H. Sanger Professorship in Oncology and is a Michael L. Rosenberg Scholar in Medical Research.

(Dr. Zhang is a Scientific Advisory Board member with Immune-Onc Therapeutics. He also owns stock in and has a sponsored research agreement with the company.)

Dr. Zhang, also a member of the Harold C. Simmons Comprehensive Cancer Center, said he is optimistic about the antibody’s treatment prospects, for multiple reasons. The LILRB4 molecule is located on the surface of cells, making it more accessible to antibody drugs. In addition, it may be possible for the treatment to combine targeted therapy directed against the cancer cells with immunotherapy using the reactivated white blood cells. Furthermore, LILRB4’s limited expression in normal cells suggests targeting it would have low toxicity for the body as a whole – an important plus for cancer treatments.

The study was funded by the National Cancer Institute, the Leukemia & Lymphoma Society, the March of Dimes Foundation, the Cancer Prevention and Research Institute of Texas, the Robert A. Welch Foundation, the National Natural Science Foundation of China, and the China Scholarship Council. 

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 2.4 million outpatient visits a year.

Story Highlights

A mouse model that develops different types of neurofibromas inside the body and on the skin allows researchers to now know the exact origin of these types of tumors. If they know where the tumor begins and the end result, they can figure out how to interrupt the development of the tumors.

DALLAS – Oct. 22, 2018 – UT Southwestern researchers have made a major advance in uncovering the biology of how thousands of disfiguring skin tumors occur in patients troubled by a genetic disorder called neurofibromatosis type 1 (NF1). This scientific advance could slow the development of these tumors.

NF1, which affects 1 in 3,000 people, has a wide spectrum of symptoms that include malignant tumors, high blood pressure, and learning disorders. While the skin tumors, which are called cutaneous neurofibromas, are most often noncancerous, they can number in the thousands and cover much of a patient’s body. They also can be painful or itchy, catch on clothing, bleed and become infected. Perhaps even more severe than the physical discomfort is the emotional distress. NF1 tumors can be severely disfiguring, like a layer of warts across the skin, and patients often dress to hide them.  

Currently, the only treatment for neurofibromas is surgical removal of the most uncomfortable and most disfiguring of the skin tumors. It would be impossible to remove them all.  

“NF1 causes significant morbidity, and an effective treatment for NF1 is long overdue,” said Dr. Lu Le, an Associate Professor of Dermatology who holds the Thomas L. Shields, M.D. Professorship in Dermatology at UT Southwestern Medical Center.  

Cutaneous neurofibromas cover the back of a patient.

“For the first time we have a mouse model that develops different types of neurofibromas inside the body and on the skin, just like in humans. Because of this model, we now know the exact origin of these two types of tumors. If you know where the tumor begins, and you know the end result, then you can follow the steps in the occurrence of the tumor and figure out how to interrupt the development of the tumors,” said Dr. Le, who treats NF1 patients as well as does research on the condition.

The researchers found that the protein Hox-B7 is a marker for the cell of origin for NF1 tumors. “It’s like a GPS system in a car. By making the Hox-B7 cells light up, we can follow the development of the tumor. It’s like branding,” said Dr. Le, the senior author of the study and a member of the Harold C. Simmons Comprehensive Cancer Center.

Another key discovery is that a parallel pathway, the Hippo pathway, can modify growth and development of these tumors. This is particularly important because treatments are being developed to block the Hippo pathway. “If you can control the Hippo pathway, you should be able to slow the development of neurofibromas, specifically in NF1 patients who also have genetic changes in their Hippo pathway,” Dr. Le said.

The research appears in the journal Cancer Discovery.

Other UT Southwestern researchers involved in this study were first author and Assistant Instructor Dr. Zhiguo Chen; postdoctoral researchers Dr. Juan Mo, Dr. Jean-Philippe Brosseau, Dr. Chung-Ping Liao, and Dr. Jonathan Cooper; research associates Tracey Shipman and Yong Wang of Dermatology; and Professor of Internal Medicine and Molecular Biology, Dr. Thomas Carroll. Dr. Carroll holds the NCH Corporation Chair in Molecular Transport.

Dr. Lu Le is a leading expert on NF1 and is working to find a medical treatment. Surgical treatment is all that is currently available.

“Research reported in this news release was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA166593.  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research was also supported by the U.S. Army Medical Research and Materiel Command, Children’s Tumor Foundation Award, Dermatology Foundation, the Giorgio Foundation, the Neurofibromatosis Therapeutic Acceleration Program, and the NF1 Research Consortium Fund.”

UT Southwestern is recognizing its 75^th year in 2018. The Harold C. Simmons Comprehensive Cancer Center, one of 49 NCI-designated Comprehensive Cancer Centers in the U.S. and the only one in North Texas, is among just 30 U.S. cancer research centers to be designated by the NCI as a National Clinical Trials Network Lead Academic Participating Site. 

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 15 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 105,000 hospitalized patients, nearly 370,000 emergency room cases, and oversee approximately 2.4 million outpatient visits a year.