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 is investigating whether cancer cells need to develop new genetic mutations in order to spread, and if some mutations happen after the cancer cells have already left the original tumor.
Progress Thus Far
Their laboratory findings suggest that the DNA in cancer cells keeps mutating after the cells have left the primary tumor. Metastatic cancer cells need a new set of mutations that are different from those that drove the primary tumor, and these mutations tend to happen in genes that play a role in helping cancer spread. Further, metastatic tumors often go through a “survival of the fittest” stage, where cancer cells with mutations that confer a survival advantage take over. The research team discovered the time it takes for cancer to come back after treatment depends on how many of these new mutations the cancer cells have when they leave the original tumor. These findings help explain why some cancers recur quickly, while others return years later.
What’s next
Dr. Chodosh and his team will study the cancer’s DNA to identify specific genes or mutations that influence how quickly metastatic tumors come back and how fast they progress once they do. They are particularly interested in PTEN, a gene that helps control cell growth, and they will explore how its loss may allow cancer cells to exit dormancy. In addition, early results suggest that some genes involved in a type of cell death and selenium-binding proteins may help cancer cells survive during dormancy and contribute to recurrence.
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.”
