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Lewis A. Chodosh, MD, PhD
Perelman Professor and Chair, Department of Cancer Biology
Abramson Family Cancer Research Institute
Perelman School of Medicine
University of Pennsylvania
Goal: To understand the mechanisms by which breast cancers develop and become resistant to therapy in order to identify potential prevention strategies.
Impact: Advances in cancer therapy have dramatically reduced the number of breast cancer deaths, but in spite of these successes, many patients will experience a recurrence. This may be due to residual cancer cells that persist and lay dormant following primary treatment for breast cancer. By studying the biology of tumor dormancy and recurrence, Dr. Chodosh hopes to identify therapeutic approaches that target residual cancer cells, thereby reducing breast cancer mortality.
What’s next: He and his team will continue to investigate why breast cancer cells lie dormant for years and then re-emerge as recurrent tumors. He is particularly interested in how obesity, weight loss, and exercise influence the likelihood of tumor recurrence.
There are more than 10 million breast cancer survivors worldwide. Despite advances in detection and treatment, up to 30 percent of patients will have recurrences with metastatic disease over their lifetimes, sometimes many years after treatment of their primary cancer. Recurrent breast cancers arise from residual dormant cancer cells that survive and persist after primary treatment. Dr. Chodosh and his team are examining the mechanism whereby these dormant cells re-emerge and resume growth.
Full Research Summary
Research area: Identifying the specific pathways and genes responsible for breast cancer recurrence and developing strategies to prevent recurrence.
Impact: Despite advances in the detection and treatment of breast cancer, up to 30 percent of patients will recur with metastatic disease over their lifetime. Recurrent breast cancers arise from the reservoir of residual cancer cells that survive and persist following primary treatment; however, it is not known how these cells are able to evade treatment and lie dormant in tissues for extended periods of time, eventually re-emerging to resume growth. Dr. Chodosh and his team are examining the mechanism whereby these dormant cells re-emerge and resume growth. Since obesity has been associated with an increased risk of breast cancer, his team is working to determine the exact role obesity plays in the reactivation of dormant cells. His results will inform behavioral and therapeutic interventions that have the potential to reduce the risk of breast cancer recurrence thereby improving the outcomes for breast cancer patients and decreasing mortality due to metastasis.
Current investigation: Dr. Chodosh and his colleagues are conducting studies to understand the mechanisms underlying tumor dormancy and recurrence and to identify the genes that play a role. In addition, his team is examining the pathways that mediate the effects of obesity, weight loss and physical activity on primary breast cancer risk and tumor recurrence.
What he’s learned so far: Dr. Chodosh has developed laboratory models to study the mechanisms associated with breast cancer recurrence and identified several genes that are expressed in dormant cells. In addition, his team has compared the genes from primary and recurrent metastatic breast cancer samples isolated from the same individual and found substantial differences. These include alterations in chromosomal and cell signaling pathways and the identification of five genes which were mutated in the metastatic samples but not in the primary samples. These genes may provide multiple targets for new treatments. In other studies, Dr. Chodosh has shown that obesity robustly and reproducibly promotes tumor recurrence in those laboratory models harboring dormant tumor cells. His results also indicate that obesity induced by a high fat diet accelerates tumor recurrence from dormant residual tumor cells.
What’s next: Dr. Chodosh is now performing genomic analyses on previously developed laboratory models to explore whether obesity alters the tumor genome from the primary tumor to recurrent tumors. In additional new studies, he will build on his finding that many of the gene expression changes that occur in recurrent tumors are immune-related and explore the potential involvement of the immune system in tumor dormancy and recurrence. Dr. Chodosh hopes to translate his findings toward designing improved clinical strategies that target tumor recurrence, a critical stage of breast cancer progression.
Dr. Lewis A. Chodosh is a physician-scientist who received a BS in Molecular Biophysics and Biochemistry from Yale University, and MD from Harvard Medical School, and a PhD. in Biochemistry from M.I.T. in the laboratory of Dr. Phillip Sharp. He performed his clinical training in Internal Medicine and Endocrinology at the Massachusetts General Hospital, after which he was a postdoctoral research fellow with Dr. Philip Leder at Harvard Medical School. Dr. Chodosh joined the faculty of the University of Pennsylvania in 1994, where he is currently a Professor in the Departments of Cancer Biology, Cell & Developmental Biology, and Medicine. Dr. Chodosh serves as Chairman of the Department of Cancer Biology, Associate Director for Basic Science of the Abramson Cancer Center, and Director of Tumor Biology for the Abramson Family Cancer Research Institute at the University of Pennsylvania. Dr. Chodosh also serves as Editor-in-Chief of Breast Cancer. His research focuses on genetic, genomic and molecular approaches to understanding breast cancer susceptibility and pathogenesis.