Titles and Affiliations
Perelman Professor and Chair, Department of Cancer Biology
Abramson Family Cancer Research Institute
Perelman School of Medicine
Research area
Addressing cancer recurrence by identifying and validating therapeutic targets unique to dormant tumor cells.
Impact
Despite advances in 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 are likely responsible for many breast cancer recurrences: the presence of residual cancer cells that survive and persist following initial treatment and tumor cell dormancy, a phenomenon whereby tumor cells lay dormant and are undetectable. While tumor dormancy and cancer recurrence are responsible for many breast cancer deaths, the mechanisms underlying these processes are not well understood. Dr. Chodosh’s research aims to deepen our understanding of these processes in order to identify interventions that can reduce the risk of breast cancer recurrence and improve long-term outcomes.
Progress Thus Far
He and his team have identified several new candidate genes that are believed to play important functional roles in tumor dormancy and recurrence. Recently, the team has focused on investigating the timing with which critical mutations in these genes occur during breast cancer recurrence. Their findings indicate that tumor cells continue to acquire clinically relevant mutations after metastatic recurrence. In their most recent work, the team discovered that a specific genetic alteration found in some patients can either prevent tumor cells from entering a dormant state after therapy or allow them to resume growth more quickly—effectively accelerating recurrence. They also found evidence that dormant tumor cells may accumulate a distinct type of genetic change that differs from those driving the original cancer, pointing toward new vulnerabilities that could be targeted therapeutically. To advance their work, the team has developed novel genetically engineered laboratory models.
What’s next
The team will utilize the previously developed laboratory models to probe the functional role of genes implicated in tumor dormancy and recurrence. Therapeutic approaches that specifically target the unique biological vulnerabilities of dormant cancer cells represent a new frontier in breast cancer research.
Biography
Lewis A. Chodosh, MD, PhD is the Chair of the Department of Cancer Biology at the Perelman School of Medicine, Associate Director for Basic Science, Director of Tumor Biology, and co-Director of the 2-PREVENT Translational Center of Excellence at the Abramson Family Cancer Research Institute at the University of Pennsylvania. He is a physician-scientist who received a BS in Molecular Biophysics and Biochemistry from Yale University, an MD from Harvard Medical School, and a PhD in Biochemistry from MIT in the laboratory of Dr. Phillip Sharp. He performed his clinical training in Internal Medicine and Endocrinology at Massachusetts General Hospital and conducted postdoctoral training 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 also serves as Editor-in-Chief of Breast Cancer Research, and he was inducted into the National Academy of Medicine in 2017.
His research focuses on the mechanisms of tumorigenesis and tumor progression, particularly with respect to the problem of breast cancer dormancy and recurrence. Dr. Chodosh has made numerous contributions to the understanding of the molecular and cellular underpinnings of cancer progression and has developed multiple genetically engineered models for human cancer that are in wide use throughout the scientific community.
“If not for BCRF, we would not have been able to help translate our laboratory findings into novel clinical trials aimed at preventing tumor recurrence in early-stage breast cancer patients by targeting dormancy pathways.”
