Bruce G. Haffty, MD

Radiation therapy remains an important component of breast cancer treatment. Despite maximal doses of radiation, selected patients, particularly younger women with breast cancer, continue to suffer local or regional relapses. One of the major components of response to radiation is a process called apoptosis or programmed cell death. A common protein, BCL-2, if over-expressed can interfere with this process resulting in failure of radiation to control the disease. Dr. Haffty has been leading studies combining novel BCL-2 inhibitor drugs with radiation and has found that the combination of radiation with the BCL-2 inhibitors results in better response rates than with radiation alone. More recently, however, this research team has discovered molecular pathways of resistance to the combination of BCL-2 inhibitors and radiation. Fortunately, these resistant pathways can also be targeted to optimize tumor response to radiation and BCL-2 inhibition. In the upcoming grant period, these investigators will explore ways to target these pathways of resistance to the combination of BCL-2 inhibition and radiation in both cell culture and laboratory models. These studies are paving the way for a clinical trial using BCL-2 inhibitors in combination with radiation and other novel available agents in patients with breast cancer.

Mid-year Progress: Dr. Haffty and colleagues continue to make progress related to the evaluation of novel molecular and genetic markers associated with failure of radiation therapy to adequately control local-regional disease, which continues to be a significant problem. Their focus has been on one of the key components of radiation sensitivity, and failure of radiation to control disease, involving the process of tumor cell death commonly referred to as apoptosis. The BCL-2 (B-Cell Lymphoma) family of proteins is central in apoptosis and has been shown to be a significant factor in the sensitivity of tumors to chemotherapy and radiation. These proteins are commonly expressed in breast cancer. Over-expression of BCL-2 is associated with decreased apoptosis and hence tumor cell survival and potential resistance to radiation and chemotherapy agents. In several studies published over the past two years with BCRF support, Dr. Haffty's team has shown that over-expression of BCL-2 related proteins are associated with increased local-regional relapse rates in patients treated for breast cancer with radiation therapy.

Fortunately, the development of orally active novel small molecule drugs that target BCL-2 provides a unique opportunity to use these drugs in combination with radiation therapy and/or chemotherapy to enhance response rates and ultimately to improve local-regional control and survival rates. In a series of experiments, Dr. Haffty and colleagues targeted BCL-2 with these novel drugs in combination with radiation, which demonstrated enhanced radiation sensitivity and increased tumor cell kill with the combination of BCL-2 targeting and radiation in breast cancers. They will continue their ongoing studies of BCL-2 and treatments targeting this family of proteins. They have already had numerous studied published related to BCRF funding. Several additional manuscripts are currently under review.

Bio:
Bruce G. Haffty, MD, is currently Professor and Chairman, Dept of Radiation Oncology, UMDNJ-Robert Wood Johnson Medical School and New Jersey Medical School and Associate Director of Clinical Sciences, Cancer Institute of New Jersey. His medical school training was at Yale School of Medicine, followed by an internship in internal medicine, residency and chief residency in the Department of Therapeutic Radiology, Yale School of Medicine, Yale-New Haven Hospital. Since completion of residency, Dr. Haffty spent the majority of his academic career at Yale School of Medicine, Department of Therapeutic Radiology, where he was a Professor of Therapeutic Radiology, served as residency program director from 1992 through 2004, Vice Chairman and Clinical Director from 2002-2005. He moved to the Robert Wood Johnson Medical School and Cancer Institute of New Jersey in 2005.

Dr. Haffty's clinical areas of expertise include breast cancer and head and neck cancer, for which he is internationally recognized. He has had numerous research grants and conducts clinical and translational research in his chosen areas of expertise. He has published over 200 peer-reviewed articles, 30 book chapters, and numerous editorials and letters. He recently completed editing a comprehensive book, Handbook of Radiation Oncology. He is consistently listed as one of the country's leading physicians by Best Doctors in America, Ladies Home Journal, Good Housekeeping, America's Top Doctors, Top Doctors for Cancer, and Top Doctors in New York and New Jersey.

In addition to a busy clinical practice, Dr. Haffty has served on numerous national committees related to research and education in radiation oncology, serves on the Editorial Board of numerous Medical Journals, and has mentored many medical students, trainees and junior faculty in conducting clinical and translational research. He is currently an Associate Editor of the Journal of Clinical Oncology, serves on the Executive Committees of the National Accreditation Program for Breast Centers and American Radium Society, and Board of Directors of ASTRO. He is co-chairman of the BOOST program for RSNA, and currently serves as Chairman of the Residency Review Committee in Radiation Oncology, and a radiation oncology Trustee of the American Board of Radiology. Dr. Haffty is President of the American Radium Society, and President-Elect of the American Board of Radiology.