Mutations in genes involved in the BReast CAncer (BRCA)-dependent DNA repair pathway represent approximately 50% of high-grade serous ovarian carcinoma. This ovarian cancer type is one of the most aggressive and difficult malignancies to treat. Precision medicine based on Poly (ADP-ribose) polymerase inhibitors (PARPi) have demonstrated promising clinical efficacy but the inevitable emergence of resistance and associated adverse side effects have limited the benefits of this therapy. Therefore, there is a pressing unmet clinical need to develop ways by which PARPi cytotoxicity and resistance can be mitigated. We have shown that depletion of an enzyme, Amplified in Liver Cancer 1 (ALC1), can hyper-sensitize BRCA-mutant ovarian cancers to PARPi. Here, we will use ALC1-deficient BRCA-mutant cancer cells to (i) identify features that can be leveraged to enhance the efficacy of PARPi and (ii) map genome regions impacted by PARPi-based therapies. Our results can help develop an innovative and promising framework to improve and predict outcomes of PARPi therapy for the high-risk group of women with BRCA-mutations who have limited therapeutic options.
Dr. Priyanka Verma is an Assistant Professor in the Division of Oncology, Department of Medicine at the Washington University, School of Medicine. She completed her Ph.D. in Biochemistry from the National Institute of Immunology, New Delhi, India. Dr. Verma pursued her postdoctoral training with Dr. Roger A Greenberg at the University of Pennsylvania where she was the recipient of an OCRA Ann and Sol Schreiber Mentored Investigator Award. Her OCRA supported research uncovered a PAR-dependent nucleosome sliding enzyme, ALC1 (Amplified in Liver Cancer 1), as a new drug target for BRCA-mutant ovarian cancers. Research in her independent group integrates several functional genomics tools to understand how PAR-dependent chromatin remodeling impacts ovarian cancer etiology and responses to targeted therapies. For her outstanding research contributions, Dr. Verma has been named as the Inaugural Pedal the Cause Researcher by Siteman Cancer Center. She has also received multiple accolades including the V-Scholar Grant, Rivkin Pilot study Grant and Mary Kay Ash Cancer Research Grant.