Experimental Therapeutics of Cancer

Mission

To identify and validate novel targets, pathways, and therapies for selective tumor targeting; to establish biomarkers that can predict tumor response; and to test the efficacy of resulting potential medicines in clinical trials.

Overview

Polymeric Micelle
Polymeric Micelle

Program leaders and members interact extensively with the Cancer Center’s disease-oriented teams to focus specific therapeutics on select cancers, based on laboratory research indicating optimal targets and relevant biomarkers.

The program's members represent key oncology disciplines and comprise basic science investigators and clinical investigators from 15 departments or centers. It is also home to the Cancer Center’s Specialized Program of Research Excellence (SPORE) in lung cancer.

Program Themes

  • Molecular therapeutic sensitizers
  • Tumor microenvironment and protein therapy
  • Imaging and drug delivery
  • Cancer vulnerabilities

Research Highlights

Specialized Program of Research Excellence (SPORE) in Lung Cancer

Stained cells
The UT SPORE in Lung Cancer studies all major forms of the disease, including (clockwise, from top left) small cell carcinoma and squamous cell carcinoma, heavily associated with smoking, and large cell carcinoma and adenocarcinoma, less strongly associated with smoking.

First awarded in 1996, the University of Texas SPORE in Lung Cancer — a collaborative effort with UT M.D. Anderson Cancer Center — leverages the talents and research of some of the world’s top lung cancer scientists, along with progress in genomics, to advance the dream of personalized medicine by moving research findings into the clinic and conveying clinical information back to the laboratory.

The UT SPORE, the largest thoracic oncology effort in the U.S., has discovered alterations between the normal-to-malignant tissue DNA of lung cancer patients that may yield new therapeutic avenues; elucidated differences between individuals that make some more susceptible to lung cancer or more likely to survive, or indicate greater risk of toxicities during treatment; described the role of cancer “stem cells” in lung cancer recurrence; and shed light on potential ways to block cancer growth, invasion, and metastasis in patients.

Selected citation: Augustyn, A. et al. ASCL1 is a lineage oncogene providing therapeutic targets for high-grade neuroendocrine lung cancers. Proc Natl Acad Sci USA 111, 14788-14793 (2014).

Beta-lapachone in pancreatic cancer

Diagram of B-lap LD-50
In NSCLC cell lines exposed to beta-lapachone (ARQ761), NQO1-positive wild-type (wt) and heterozygous (hets) cells are killed (top) irrespective of mutations (red, blue) in oncogenic drivers or passengers (bottom). In contrast, NQO1-negative cells with polymorphisms (pm) in the gene are resistant (top right) (Huang et al., 2014).
Click on image to see enlarged version. 

Foundational research by the laboratory of Dr. David A. Boothman on the anti-cancer effects of the natural substance beta-lapachone has led to two major, multidisciplinary projects testing the substance against pancreatic ductal adenocarcinoma (PDA) and non-small cell lung cancer (NSCLC). The first project is pursuing laboratory studies and a phase IB clinical trial involving standard-of-care chemotherapy plus a formulation of beta-lapachone known as ARQ761 (from the biotechnology companies NQ Oncology and ArQule). The project’s lab studies include noninvasive, real-time metabolic imaging of pancreatic cancer in animals using hyperpolarized glucose or pyruvate to better understand ARQ761’s impact on tumor metabolism. The effort also includes examination of biomarkers associated with pancreatic tumors that might predict response to ARQ761 or reflect the treatment’s impact. The other project is exploring the efficacy of combining ARQ761 with PARP (poly[ADP-ribose] polymerase) inhibitors to treat PDA and NSCLC, as well as all other NQO1 over-expressed malignancies. The combination has previously proved effective against pancreatic, breast, and non-small cell lung cancer cells in vitro (see figure), as well as non-small cell lung cancer in mouse xenografts.

Selected citation: Chakrabarti, G. et al. Targeting glutamine metabolism sensitizes pancreatic cancer to PARP-driven metabolic catastrophe induced by beta-lapachone. Cancer Metabolism 3, 12 (2015).

News release: Substance in tree bark could lead to new lung cancer treatment

Stereotactic ablative radiotherapy (SABR)

CAT scan
SABR plan for treating a lung cancer

Groundbreaking work by Dr. Robert Timmerman and colleagues, spanning two decades, has demonstrated the benefits of SABR (also known as stereotactic body radiotherapy, or SBRT) in treating a number of tumor types. In SABR, highly focused beams of radiation are fired from numerous angles, converging to deliver a high therapeutic dose to a tumor target. Among the team’s noteworthy successes are using SABR to treat early-stage lung tumors in frail patients, and in limited metastatic lung cancer. The therapy is also proving promising in treating “radioresistant” tumors such as renal cancer and melanoma, and for inferior vena cava tumor thrombus, an often deadly complication of kidney cancer.

News releases:

To Get Involved

ET Program meetings are held quarterly, with Laboratory Correlate meetings for biomarker development every second Thursday of each month. The program seeks additional physicians and scientists with broad understanding of molecular events leading to human cancers for further collaborative research projects.

Contact Dr. Boothman for more details about the program, meetings, and more. david.boothman@utsouthwestern.edu

Selected Publications