Nanoparticles shrink and kill cancer tumors

By Alex Lyda

Dr. David Boothman

What if an oncologist could inject small particles into a patient that quickly sought out cancer tumors, and just as quickly started a chain reaction in which tumor cells entered a death spiral?

And unlike traditional radiation treatments, which can harm both healthy and cancerous tissues indiscriminately, what if these chemical nanoparticles killed cancer cells only, leaving healthy ones intact and functioning normally?

Triggering a so-called “kiss-of-death” reaction within cancer cells is now within reach of the laboratories of Dr. David Boothman, Professor of Radiation Oncology and Pharmacology, and Dr. Jinming Gao, Professor of Pharmacology. Both researchers are associated with the Harold C. Simmons Comprehensive Cancer Center.

Dr. Boothman and his colleagues in the Cell Stress and Cancer Nanomedicine Program at UT Southwestern Medical Center are developing nanoparticles specifically designed to break down cancer cell resistance and recovery responses to the “stressful insults” that occur after chemotherapy or radiation therapy.

The program has developed nanoparticles capable of delivering a novel class of two known drugs, one of which, ß-lapachone, is derived from the bark of the Lapacho tree found in the South American Rainforest. These drugs can selectively and quickly kill cancer cells that have elevated levels of an enzyme called NQO1, found mostly in abundance in solid tumors.

Dr. Boothman teamed up with Dr. David Gerber, Assistant Professor of Internal Medicine, to develop a clinical trial ongoing within the Simmons Cancer Center to analyze the safety of using the drug ARQ 761, a derivative of ß-lapachone. Early on, Dr. Gerber also became interested in what the natural product did in the body as it targets elevated NQO1 levels that are typically higher in patients with breast, prostate, non-small cell lung, pancreatic, and colon cancers.

The UTSW group, along with Dr. Paul Hergenrother of the University of Illinois at Urbana-Champaign, reported in Cancer Research that another new drug was just as or more effective against human solid cancers, including pancreatic cancers. This new drug, deoxynyboquinone, was better at exploiting NQO1 for cell death responses and is now under Phase I clinical trials at UT Southwestern.

Dr. Boothman recently received a $200,000 grant from the Pancreatic Cancer Action Network and the American Association for Cancer Research for this targeted approach to treating pancreatic cancer. It is the first time that UT Southwestern has been given the award.

“Causing DNA damage specifically to cancer cells and then blocking their ability to repair themselves will hopefully increase the effectiveness of these novel therapeutic agents,” Dr. Boothman said. “When exposed to certain compounds, cancer cells try to repair and evade these treatments in order to survive and spread. Understanding these cell stress events at a molecular level, including the DNA repair inhibitors required for cancer cells to evoke a resistance pathway, has ultimately allowed us to exploit these pathways for improved cancer-selective therapies.”

Another important advantage for patients is that studies suggest this nanoparticle treatment could take only two hours to reach and treat tumor targets. That compares to the repeated and prolonged infusions many chemo patients know and dread.

Speed is important in killing certain types of cancer, particularly those of the pancreas, which often are diagnosed only in later stages of the disease. Actor Patrick Swayze waged one of the more famous and public pancreatic cancer battles, dying 20 months after receiving a diagnosis of Stage IV pancreatic cancer in 2008.

“Considering the limited treatment options for pancreatic cancer, finding novel drugs to fight this dreaded set of diseases is the focused goal of researchers at UT Southwestern,” said Dr. James Willson, Director of the Simmons Cancer Center.

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Dr. Boothman holds Robert B. and Virginia Payne Professorship in Oncology.

Dr. Willson holds the Lisa K. Simmons Distinguished Chair in Comprehensive Oncology.

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