Johns Hopkins University School of Medicine Baltimore, Maryland
The Peter and Judy Kovler Professor in Breast Cancer Research, Department of Pathology Director, Pathology and Breast Pathology Johns Hopkins Medicine National Capitol Region
Determining which breast cancer patients will respond to PARP inhibitors and identifying strategies to improve PARP inhibitor effectiveness for more patients.
BRCA-driven breast cancers have a distinctive feature associated with defects in DNA repair. This leads to frequent DNA damage events resulting in genomic instability, which makes tumors very aggressive. While this feature makes the tumor cells very mutable and thus adaptable, it also makes them vulnerable to a class of drugs called PARP inhibitors as well as other DNA damaging agents, because the cells cannot repair the DNA damage. Unfortunately, tumors develop resistance to these drugs by activating alternative DNA repair pathways. Dr. Richardson’s research is focused on understanding how defects in different DNA repair pathways cause either sensitivity or resistance to anti-cancer drugs like PARP inhibitors. This research could lead to a new way to test mutations in other rare DNA repair genes and prognostic biomarkers to predict sensitivity to particular drugs.
Dr. Richardson and her team examined how specific mutations in the BRCA1 gene affect a tumors cell’s response to PARP inhibitor treatment. They identified a specific region of the gene that when mutated made breast cancer cells sensitive to PARP inhibitor treatment. Likewise, they showed that a gene called 53BP1 interacts with the BRCA1 gene in regulating multiple aspects of DNA repair. Dr. Richardson and her colleagues are now focused on one aspect of the DNA repair process called translesion synthesis. They have developed a series of laboratory models to gain a better understanding of what role translesion synthesis plays in BRCA-driven tumor development and sensitivity to treatments.
In the coming year, Dr. Richardson plans to extend her studies to examine the roles BRCA1 plays in genomic instability and to drill down on different parts or domains of the BRCA1 protein and their roles in the development of PARP inhibitor resistance. This research will inform our understanding of how inherited mutations in DNA repair genes lead to further mutations in tumor DNA and potentially reveal new ways to target this function and hinder breast cancer formation.
Dr. Andrea L. Richardson is an Associate Professor of Pathology and Director of the Pathology Community Practice Division at Johns Hopkins University School of Medicine, where she moved in 2015 after more than eight years on the faculty of Brigham and Women’s Hospital, Harvard Medical School in Boston. She maintains an active clinical practice on the breast pathology consultation service. Her research focus is breast cancer genetics and pathobiology. She is actively engaged in translational breast cancer research, frequently with multi-disciplinary teams. Dr. Richardson has extensive experience in tissue-based molecular assays. Her laboratory research has focused on characterizing the molecular aberrations in subtypes of breast cancer important for pathogenesis, tumor progression, and tumor response to therapy.
2007
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