Grants totaling $2.76 million give six physician-scientists resources to pursue cancer research

(New York, NY)  The Damon Runyon Cancer Research Foundation announced that six physicians with novel approaches to fighting cancer have been named the 2019 recipients of the Damon Runyon Physician-Scientist Training Award. The awardees were selected through a highly competitive and rigorous process by a scientific committee comprised of leading cancer researchers who are themselves physician-scientists. Only those scientists showing bold initiative and a commitment to finding new cures for cancer were selected to receive the award. 

Physician-scientists are crucial to moving scientific discoveries from the lab to patients, but only one percent of all doctors are physician-scientists. That number is at risk of shrinking further, due to lack of funding. Fewer MDs are choosing to go into research because the career path is challenging and the remuneration lower than clinical practice. To help increase the number of physician-scientists, the Damon Runyon Cancer Research Foundation created the Damon Runyon Physician-Scientist Training Award, which provides physicians who have earned an MD degree and completed clinical specialty fellowship training the opportunity to gain the research skills and experience to become leaders in translational and clinical research. To address the financial burdens that often deter physicians from pursuing a research career, Damon Runyon provides significantly higher funding than most research fellowships—$460,000 over four years. The award also retires up to $100,000 of medical school debt still owed by an awardee (the average medical school debt is now more than $200,000.)

“Physician-scientists have the unique ability to blend their insights from treating patients and working in the laboratory in a way that enables and accelerates medical advances,” said Yung S. Lie, PhD, President and Chief Executive Officer of the Damon Runyon Cancer Research Foundation. “If the current shortage of physician-scientists continues, we risk a situation in which major laboratory research discoveries may not reach patients at all, and that would represent a true crisis in cancer research.”

The Physician-Scientist Training Award was established in 2015 thanks to the generosity of Damon Runyon Board Members Leon Cooperman and Michael Gordon.

2019 Damon Runyon Physician-Scientist Training Award Recipients:

Edmond M. Chan, MD, with mentor Adam J. Bass, MD, at Dana-Farber Cancer Institute, Boston, MA

Defects in the cellular DNA repair machinery can promote cancer formation and cause cancer cells to rely on back-up DNA repair processes. These cancer cells are particularly vulnerable to drugs called PARP inhibitors, which target a DNA repair process known as homologous recombination. Dr. Chan hypothesizes that a similar treatment strategy can be used for cancers with deficiencies in DNA mismatch repair, which causes microsatellite—short, repeated sequences of DNA—instability (MSI). Microsatellite instability is found most often in certain colon, stomach, uterine and ovarian cancers. Using CRISPR screening technology, Dr. Chan discovered that cancer cells with faulty mismatch repair become dependent on a gene called WRN to survive. He is characterizing this vulnerability for MSI cancers with the goal of finding new drugs that inhibit this pathway.

Andrew J. Dunbar, MD, with mentor Ross L. Levine, MD, at Memorial Sloan Kettering Cancer Center, New York, NY

Mutations in the cancer-causing oncogene JAK2 are a hallmark of myeloproliferative neoplasms (MPNs), a blood disorder characterized by over-production of mature blood cells. While currently available JAK2 inhibitors improve symptoms, they are unsuccessful at completely eradicating diseased cells, so remissions are rare. Using genetically engineered mice, Dr. Dunbar will investigate how MPN cells remain dependent on JAK2 signaling for cell growth, and how additional mutations in the epigenome (the proteins involved in regulating gene expression) might contribute to drug resistance. His research aims to identify improved JAK2 inhibitors and lend insight into whether targeting both oncogenic drivers and epigenetic defects could be required for effective therapy. Ultimately, he hopes these findings will translate into better treatments for patients with these cancers.

Gabriel K. Griffin, MD, with mentors Bradley E. Bernstein, MD, PhD, and Arlene H. Sharpe, MD, PhD, at Brigham and Women's Hospital, Boston, MA

Immunotherapy drugs, which spur the body's own immune system to attack tumors, hold great promise but still fail in many patients. Dr. Griffin aims to identify therapeutic targets that can enhance the efficacy and scope of immunotherapy in melanoma and other cancer types. His unique approach focuses on retrotransposons, repetitive sequences of DNA that are evolutionary remnants of viruses and comprise upwards of 50% of the human genome. These genetic elements are usually silenced via DNA methylation but can activate an immune response at certain times. Dr. Griffin’s research will characterize the epigenetic pathways that silence these repetitive elements in cancer cells, thus helping tumors evade surveillance by the immune system. This basic understanding may guide the development of epigenetic therapies capable of triggering anti-tumor immunity.

Ashley K. Koegel, MD, with mentors Wendell A. Lim, PhD, and Mignon Loh, MD, at the University of California, San Francisco, CA

Acute myeloid leukemia (AML), the most common type of blood cancer, is curable in less than 30% of all patients. Recently, chimeric antigen receptor (CAR) T cell therapy has successfully cured patients with certain types of leukemia. This approach has not yet been effective for treatment of AML, in part because these cells look very similar to certain types of healthy blood cells that are critical for life. Dr. Koegel has engineered a variety of scientific tools (specific receptors) that can be used to develop next-generation CAR-T cells that can effectively kill AML cells without significant toxicity to normal, healthy blood cells. The first receptor acts as an ON/OFF switch and is regulated by a small molecule drug. The T cell is turned ON only in the presence of the small molecule. The second receptor allows T cells to discriminate AML cells from healthy blood cells. Successful next-generation immunotherapy strategies will provide AML patients with much needed treatment options.

Jonathan E. Shoag, MD, with sponsor Christopher E. Barbieri, MD, PhD, at Weill Cornell Medicine, New York, NY

Prostate cancer is the second leading cause of cancer death in men in the United States. Remarkably, work over the past decade has demonstrated that even the worst prostate cancers are dependent on the same signaling pathways that govern normal prostate behavior. Dr. Shoag’s objective is to identify drugs that have activity against the normal prostate and can be used to understand and treat prostate cancer. Dr. Shoag will apply novel statistical and machine learning approaches on large scale clinical data to discover new therapies and pathways important in prostate cancer. He will then test these therapies in genetically engineered and patient-derived prostate cancer models. Identifying active drugs against prostate cancer that are already FDA-approved or have been previously studied in clinical trials for other cancers can aid in understanding prostate cancer biology and can rapidly benefit patients with advanced disease.

Rabi Upadhyay, MD, with mentor Dan R. Littman, MD, PhD, at New York University School of Medicine, New York, NY

Immunotherapies using checkpoint inhibitors have shown amazing results in certain solid cancers. However, there are vast differences in treatment outcomes for patients who have remarkably similar cancers (based on histology and genetics) and many patients develop resistance. In addition, predicting who will benefit from the treatment has been unreliable. Recent research found that the diversity and specific quality of microbes that colonize the intestines (the gut microbiome) can impact the success of cancer immunotherapy, but there is no consensus about the underlying mechanisms. Dr. Upadhyay aims to build a mouse model of lung cancer that replicates the previous findings and then dissect the intricate biology between the gut microbiota and tumors in the lung. He plans to further define the cells and molecules involved, with the hope that more effective immunotherapy treatments can be designed for patients.