Posted September 24, 2013
Panagiotis Konstantinopoulos, M.D., Ph.D., Dana-Farber Cancer Institute
Ovarian tumors with BRCA1 or BRCA2 germline mutations are especially sensitive to platinum analogues and PARP inhibitors, resulting in increased survival rates for women with these tumors. It has been shown that certain sporadic, or non-genetic, tumors share this "BRCAness" phenotype. Prospective identification of sporadic tumors with the BRCAness phenotype is important to the appropriate clinical management of women bearing these tumors. Dr. Panagiotis Konstantinopoulos, a Fiscal Year 2009 Early Career Investigator in the DoD Ovarian Cancer Academy, developed a gene expression profile that can identify tumors with the BRCAness phenotype and demonstrated that these BRCA-like tumors are more sensitive to platinum and PARP inhibitors. Recently, he identified that expression of certain microRNAs, a class of gene expression regulators, was associated with enhanced sensitivity to platinum and PARP inhibitors and with improved survival outcomes in ovarian tumor samples. Dr. Konstantinopoulos hypothesizes that these microRNAs may downregulate genes involved in homologous recombination, an element of DNA repair that is often defective in cancer cells. His work on BRCAness and miRNAs aims to improve our understanding of responsiveness to chemotherapy in ovarian cancer, expand the cohort of patients who may benefit from novel agents such as PARP-inhibitors, and help detect BRCA-like ovarian tumors to facilitate a personalized treatment approach that may improve survival and quality of life for women with this disease.