New York, NY, June 12. 2012 The Damon Runyon Cancer Research Foundation named six new Damon Runyon Clinical Investigators at its spring 2012 Clinical Investigator Award Committee review. The recipients of this prestigious three-year award are outstanding early career physician-scientists conducting patient-oriented cancer research at major research centers under the mentorship of the nation's leading scientists and clinicians. Each will receive $450,000 to support the development of his/her cancer research program.
The Foundation also awarded Continuation Grants to two Damon Runyon Clinical Investigators. Each award will provide an additional two years of funding totaling $300,000. The Continuation Grant is designed to support Clinical Investigators who are approaching the end of their original awards and need extra time and funding to complete a promising avenue of research or initiate/continue a clinical trial. This program is possible through the generous support of the William K. Bowes, Jr. Foundation, and Connie and Robert Lurie.
The Clinical Investigator Award program is specifically intended to help address the shortage of physicians capable of translating scientific discovery into new breakthroughs for cancer patients. In partnerships with industry sponsors and through its new Accelerating Cancer Cures initiative, the Damon Runyon Cancer Research Foundation has committed more than $41 million to support the careers of 64 physician-scientists across the United States since 2000.
2012 Clinical Investigator Awardees
Carey K. Anders, MD
There are multiple different subtypes of breast cancer defined by distinct tumor characteristics and unique clinical consequences. Among women with advanced HER2-positive breast cancer, one of the more aggressive subtypes, recurrence of the cancer in the brain is commonoccurring in approximately 30% of patients. Presently, there are systemic therapies capable of controlling HER2-positive breast cancer in most parts of the body; however, there are very few agents capable of crossing the blood-brain barrier and controlling HER2-positive breast cancer that has spread to the brain, or brain metastases.
Dr. Anders is focused on improving survival for women with breast cancer brain metastases. She has identified a promising therapeutic target: the PI3K/mTOR pathway, which is highly expressed in a panel of breast cancer brain metastases. Everolimus (Afinitor), a small molecule inhibitor drug of mTOR, has shown activity in advanced HER2-positive breast cancer and crosses the blood-brain barrier. She has developed a Phase II, multi-center clinical trial evaluating the efficacy and safety of everolimus in combination with chemotherapy and HER2-directed therapy to treat women with progressive HER2-positive breast cancer brain metastases. She will conduct analyses to identify gene and protein expression patterns that may reflect response or resistance to this combination therapy. Her goals are to provide a novel therapy for women who, at present, have few therapeutic options, while laying the foundation for future clinical trials incorporating biomarkers to enhance therapeutic response and survival for women with HER2-positive breast cancer brain metastases.
Dr. Anders works under the mentorship of Lisa A. Carey, MD, and Charles M. Perou, PhD, at the University of North Carolina, Chapel Hill, North Carolina.
Oren J. Becher, MD
Diffuse intrinsic pontine glioma, or DIPG, is an incurable brain cancer that mostly strikes young children. The median survival rate is less than one year after diagnosis. To date, there are no chemotherapeutic or targeted agents that have proven to be beneficial for treatment of these cancers.
Dr. Becher leads one of very few laboratories around the world that focus exclusively on this type of deadly brain cancer. He is using a novel DIPG mouse model to study the function of proteins that drive tumor growth and to determine how novel anti-cancer drugs can inhibit tumor growth. His goal is to identify the most effective drugs against this type of brain cancer and then translate these findings by testing the drugs in clinical trials for children afflicted with this type of brain cancer.
Dr. Becher works under the mentorship of Darell D. Bigner, MD, PhD, and Katherine E. Warren, MD at Duke University, Durham, North Carolina.
Sarat Chandarlapaty, MD, PhD
The PI3K/AKT/mTOR signaling pathway normally conveys cues from the cell's environment into programs that promote cellular growth, division, and motility. Components of the PI3K signaling pathway are mutated in greater than 70% of all breast cancers and promote the persistent and exaggerated cell growth that is necessary for tumor formation and survival. This pathway is therefore a promising target for treating breast cancers; however, drugs designed to target the PI3K signaling pathway are initially effective but resistance rapidly develops.
Dr. Chandarlapaty seeks to understand how tumor cells rapidly adapt to PI3K inhibitor drugs. His initial studies indicate that cancer cells use a cellular mechanism called "negative feedback" to either activate alternative signaling pathways not blocked by the drug or reactivate the PI3K pathway. His goal is to identify other targets that can be blocked in combination with the PI3K pathway to more effectively kill cancer cells but not normal cells. These combinations will be tested in clinical trials in breast cancer patients with mutations in the PI3K pathway.
Dr. Chandarlapaty works under the mentorship of Neal Rosen, MD, PhD, and Clifford A. Hudis, MD, at Memorial Sloan-Kettering Cancer Center, New York, New York.
Ryan B. Corcoran, MD, PhD
Mutations in the BRAF gene occur in 10-15% of colorectal cancers and predict poor outcome. Drugs that block the action of mutant BRAF are under active clinical development, and one drug that blocks BRAF was recently approved by the Food and Drug Administration (FDA) for treatment of metastatic melanoma. However, these BRAF inhibitor drugs alone have not been effective in BRAF mutant colorectal cancer patients, suggesting that improved approaches are needed.
Dr. Corcoran's goal is to develop new treatment strategies for BRAF mutant colorectal cancer. Through a combination of laboratory studies and clinical trials, he plans to identify other key survival signals in BRAF mutant colorectal cancers that can be targeted, in combination with BRAF inhibitors, to improve treatment response in BRAF mutant colorectal cancer patients. Ultimately, he aims to develop novel effective treatments for patients with this lethal subtype of colorectal cancer.
Dr. Corcoran works under the mentorship of Jeffrey A. Engelman, MD, PhD, and Keith T. Flaherty, MD, at Massachusetts General Hospital, Boston, Massachusetts.
Kevin B. Jones, MD
Every cell in the human body is held in a balance between signals that will initiate a program of cell death called apoptosis at any sign of internal stress and opposing signals that promote survival of the cell. Cancer cells harbor many internal stresses and often depend on very powerful cell-survival-promoting signals to keep the strong cell-death signals in check.
Synovial sarcoma is a cancer that primarily targets adolescents and young adults. Although rare, the young age of its victims greatly increases the importance of this cancer as it too often takes them in the prime of life; five-year survival rates remain quite low. Synovial sarcoma has an unusual balance of cell-death signals and cell-survival signals that makes it very resistant to many chemotherapies used to try to kill the tumor. Dr. Jones aims to improve understanding of this unique balance, with the goal of learning how to topple it in favor of killing tumor cells and thus increasing patient survival. His discoveries will be directly pertinent to synovial sarcoma, but will also likely impact cancer research more generally through its findings about apoptosis.
Dr. Jones works under the mentorship of Mario R. Capecchi, PhD, and Sunil Sharma, MD, at the University of Utah, Salt Lake City, Utah.
Holbrook E. Kohrt, MD, PhD
Monoclonal antibodies that target cancer are among the most notable scientific advances of the last quarter century. Rapid translation of this research has prolonged the survival of thousands of patients with lymphomas that express CD20, breast cancers that express HER2, and colorectal, lung, and head and neck cancers that express EGFR. Despite the promising activity of antibodies such as rituximab (Rituxan, targets CD20), trastuzumab (Herceptin, targets HER2), and cetuximab (Erbitux, targets EGFR), the response rate among patients with advanced cancer remains suboptimal at less than 25%.
Antitumor activity of monoclonal antibodies is dependent, in part, upon the immune response, which recognizes and destroys antibody-bound tumor cells. Dr. Kohrt will focus on developing new therapies that improve the activity of monoclonal antibodies, with the ultimate goal of eliminating the need for chemotherapy as a treatment for cancer patients. He recently identified an antibody that targets activated immune cells and enhances the cells' function, leading to increased destruction of the targeted cancer cells. His work will include a Phase I clinical trial testing this novel immune-enhancing antibody in patients.
Dr. Kohrt works under the mentorship of Ronald Levy, MD, at Stanford University, Stanford, California.
2012 Clinical Investigator Continuation Grants
Andrew L. Feldman, MD
Dr. Feldman's research focuses on defining the role of the transcription factor IRF4 in T-cell lymphomas (TCLs), aggressive cancers that are fatal in the majority of patients. He proposes that IRF4 represents a rational therapeutic target for TCLs and aims to develop new strategies to block IRF4 in lymphoma cells. Novel targeted therapies for TCL could greatly improve the outcome for patients with this disease.
The Continuation Grant will enable Dr. Feldman to pursue translational studies examining a newly discovered subset of TCLs with IRF4 mutation as well as rearrangement of another gene called TP63. He hypothesizes that these genetic features could be used to stratify patients with TCLs; these patients are likely at high risk and should be treated with intensified regimens.
Dr. Feldman works under the mentorship of Stephen M. Ansell, MD, PhD, and Ahmet Dogan, MD, PhD, at the Mayo Clinic, Rochester, Minnesota.
William Y. Kim, MD
Renal cell carcinoma (RCC) is a type of kidney cancer that has a poor prognosis when diagnosed at later stages. RCC patients treated with drugs that block the protein mTOR have prolonged overall survival, yet the tumor does not shrink. The current complete remission rate with existing therapies remains low. Dr. Kim [Damon Runyon-Merck Clinical Investigator] hypothesizes that targeting other pathways in combination with mTOR could be an effective treatment strategy. He will use the Continuation Grant to identify new drug combinations by applying novel proteomic technologies. His goal is to rapidly move these findings to the clinical setting for improved treatment of RCC.
Dr. Kim works under the mentorship of Charles M. Perou, PhD, and Norman E. Sharpless, MD, at the University of North Carolina, Chapel Hill, North Carolina.
|Contact: Yung S. Lie, PhD|
Damon Runyon Cancer Research Foundation