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Charles M. Perou, PhD
May Goldman Shaw Distinguished Professor of Molecular Oncology Research
Professor of Genetics & Pathology
Lineberger Comprehensive Cancer Center
University of North Carolina
Chapel Hill, North Carolina
Goal: To identify the genetic alterations that underlie aggressive subtypes of breast cancer.
Impact: Dr. Perou is using advanced technologies to understand the interaction of immune cells with tumor cells and how this varies across tumor subtypes. His studies may lead to improvements in diagnosis and the development of new therapies for patients who have aggressive subtypes of breast cancer.
What’s next: He and his team will build upon their work by examining the diversity of immune cell types that are present in breast tumors. They will also continue to develop computational models that may predict how individual patients will respond to therapy.
Breast cancer is not a single disease. Rather, it is a collection of diseases, some of which have a poorer prognosis than others and vary in their response to treatment. Dr. Perou’s research is focused on identifying the genetic alterations that give rise to subtypes of breast cancer that have a worse prognosis—work he hopes will reveal biomarkers that can be used to both guide treatment and inform the development of novel therapies
Full Research Summary
Research Area: Identifying the causative genetic alterations that give rise to aggressive breast cancers and using this information to guide therapeutic targeting of these cancer-causing events.
Impact: A goal of precision medicine is to identify cancer-causing events and use this information to inform the right treatment for each patient. This necessitates both drug development and the identification of biomarkers to guide therapy choices. Dr. Perou and his team are focusing on identifying the causative genetic alterations that give rise to those breast cancers with the worse prognosis. Results from these studies will guide the therapeutic targeting of these cancer-causing events.
Current investigation: He and his colleagues are conducting studies on aggressive breast cancer subtypes with a focus on the role of the immune system.
What he’s learned so far: They have found that the immune system plays a role in the expression of different breast tumor subtypes, suggesting that the immune system is recognizing specific tumor antigen(s). Using laboratory models, they have learned that B-cells (a specific type of immune cell) play an active role in the response of breast cancer cells to multiple therapies currently in use – chemotherapy, trastuzumab and immune checkpoint inhibitors (ICI). Their laboratory experiments have shown that when B-cells are depleted, ICI treatment is ineffective. Thus, B-cells may provide novel targets for therapy or biomarkers of response and patient outcomes.
What’s next: The team will continue to characterize the differences in breast tumor landscape, tumor biology and the immune microenvironment of aggressive breast tumor subtypes. The team will explore the diversity of immune cell types that are present within breast tumors and identify some of the tumor antigen(s) that are targets of the immune system, particularly B-cell targets. In addition, they will continue to build computational models as predictors of prognosis and response to chemotherapy and immunotherapy.
Dr. Perou is a member of the Lineberger Comprehensive Cancer Center at UNC, and the Scientific Director of the UNC Bioinformatics Core. He received his PhD in Cellular and Molecular Biology from the Department of Pathology at the University of Utah (1996) where he cloned the human Chediak-Higashi Syndrome gene. He next performed his postdoctoral training in the laboratory of David Botstein at Stanford University (1997-2000) where he began his genomic studies of human tumors using DNA microarrays. These genomic analyses resulted in the identification of novel subtypes of human breast tumors that predict patient survival times and response to therapy. Dr. Perou's laboratory at UNC is focused on using genomics, genetics, and laboratory models to decipher the underlying biology of the molecular subtypes of breast cancer. He then uses this biological information to develop novel therapeutic strategies that are specifically targeted against each of these distinct subtypes of breast cancer.