2008 Program Project Development Grant Recipient – Robert C. Bast
Robert C. Bast, Jr., M.D.
MD Anderson Cancer Center
Autophagy and Ovarian Cancer
In a process called autophagy, or “self eating,” normal cells break down their component proteins and fats in the membranes and organelles that have worn out. Autophagy also acts as a survival mechanism to generate, in the short run, energy for the cell when sugar and other nutrients are limited. But when autophagy is prolonged, cells die. Dr. Bast has found that autophagy also occurs in ovarian cancer cells. Following surgery and chemotherapy, small nests of ovarian cancer cells can remain dormant on the surface of the abdominal cavity for years, growing progressively and leading to the death of the patient. In the absence of a blood supply, autophagy provides the energy to keep these ovarian cancer cells dormant. In addition, certain protein “survival factors” are produced in or near the tumor nests that prevents prolonged autophagy from killing the cancer cell. Dr. Bast believes that by blocking autophagy or by neutralizing survival factors, it should be possible to eliminate dormant ovarian cancer cells. His research examines the mechanisms of autophagy in ovarian cancer. His findings may lead to new treatments for ovarian cancer.
Dr. Bast is Vice President for Translational Research at the UT M.D. Anderson Cancer Center. His office facilitates translation of new strategies, drugs and devices from laboratory to the clinic, as well as the movement of human material and data from the clinic to laboratory. Dr. Bast received his B.A. cum laude from Wesleyan University and his M.D. magna cum laude from Harvard Medical School. After completing a medical internship at the Johns Hopkins Hospital, he served as a research associate at the National Cancer Institute. Returning to Boston, Dr. Bast completed a medical residency at the Peter Bent Brigham Hospital and a fellowship in Medical Oncology at the Dana-Farber Cancer Institute. He joined the faculty at Harvard as an Assistant Professor and was subsequently appointed Associate Professor at the Dana-Farber Cancer Institute. Dr. Bast was recruited to the Duke University Medical Center in 1984 as Professor of Medicine, Microbiology and Immunology to Co-Direct the Division of Hematology-Oncology and to serve as Clinical Director of the Cancer Center. In 1987, he became the Director of the Duke Comprehensive Cancer Center and in 1992 he was named Wellcome Clinical Professor of Medicine in Honor of R. Wayne Rundles. In July 1994, Dr. Bast was recruited to head the Division of Medicine at UT M. D. Anderson Cancer Center and to fill the Harry Carothers Wiess Chair for Cancer Research. In 2000, Dr. Bast was appointed Vice President for Translational Research. In 2004, he became the Harry Carothers Wiess Distinguished University Professor for Cancer Research.
Dr. Bast is best known for developing the OC125 monoclonal antibody that led to the production of the CA125 radioimmunoassay. Serum CA125 levels have provided the first generally useful marker for monitoring the course of patients with epithelial ovarian cancer. CA 125 is currently being evaluated as one component of a screening strategy for ovarian cancer. His early studies focused on the use of immunostimulants and monoclonal antibodies for cancer therapy. Over the last 15 years his group has pioneered in defining molecular alterations in ovarian and breast cancers that might serve as targets for therapy as well as diagnosis. His most recent studies have focused on the identification of ARHI, a novel ras-related imprinted tumor suppressor gene that induces autophagy and tumor dormancy. He has led the U.T. M.D. Anderson SPORE in Ovarian Cancer since 1999. Overall, Dr. Bast has published more than 500 articles and chapters, and has edited the textbook Cancer Medicine. He has been recognized by Institute for Scientific Informal as one of the most frequently cited scientists in his field. In 2006 he was recognized with the Smith-Klein Beacham Clinical Laboratories Award, the ISOBM-Abbott Award and an Award for Excellence in Gynecologic Oncology by the International Society of Gynecologic Oncology. He continues to care for patients with breast and ovarian cancer and has been listed in the Best Doctors of America and in America’s Top Physicians.