Titles and Affiliations

Perelman Professor and Chair, Department of Cancer Biology
Abramson Family Cancer Research Institute
Perelman School of Medicine
University of Pennsylvania
Philadelphia, Pennsylvania

Research area

Identifying the specific pathways and genes responsible for drug resistance and breast cancer recurrence to develop prevention strategies. 

Impact

Despite advances in detection and treatment, up to 30 percent of patients will experience a breast cancer recurrence with metastatic disease over their lifetimes, sometimes many years after treatment of their primary cancer. Two factors, the presence of residual disease and tumor cell dormancy—a phenomenon whereby tumor cells lay dormant and are undetectable—are likely responsible for many breast cancer recurrences. The mechanisms underlying these processes, however, are largely unknown. Dr. Chodosh is working to identify interventions for breast cancer survivors that can reduce the risk of recurrence and improve long-term outcomes. In his current BCRF research, he is exploring the biological underpinnings of the effects of obesity, weight loss, and exercise on breast cancer recurrence. Dr. Chodosh’s team developed novel laboratory models that recapitulate the effects of obesity, exercise, and caloric restriction on both residual cancer and tumor-cell dormancy. Using these models, they showed that a high-fat diet promoted the survival of disseminated and dormant tumor cells. His team is evaluating the mechanisms involved and hopes their findings will enable the design of behavioral and therapeutic interventions with the potential to prevent tumor recurrence and reduce the mortality associated with metastatic breast cancer. 

Progress Thus Far

Using his novel experimental models, Dr. Chodosh’s team has identified five classes of genes  that may play a functional role in tumor cell dormancy and breast cancer recurrence. Other studies comparing the genomic data from patient-matched primary and recurrent metastatic breast cancers  revealed that five genes were mutated in the metastases but not in the primary cancers. In the last year, Dr. Chodosh’s research has indicated that many of the gene expression changes that occur in recurrent tumors are immune-related.

What’s next

Dr. Chodosh and his colleagues will continue to delve into the data comparing primary and recurrent metastases. His studies have revealed multiple therapeutic targets for preventing metastatic recurrence. Building on their findings, his team will functionally test the role of these candidates in tumor dormancy and recurrence to reduce the burden of residual tumor cells and prevent or delay tumor recurrence.

Biography

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.

BCRF Investigator Since

2003

Donor Recognition

The William P. Lauder Awards