Priyanka Verma, PhD
Washington University, St. Louis
2022 MCM Pilot Study Award
Targeting drug resistance in BRCA-mutant ovarian cancers by exploiting endogenous base damage
Many ovarian cancers are caused by mutations in proteins that usually function to repair DNA damage. These cancer cells with accumulated DNA damage are targeted by PARP inhibitor therapies. Despite ovarian tumors showing an excellent clinical response to PARP inhibitors initially, tumors inevitably develop resistance. Dr. Verma is taking an innovative approach to overcoming the clinical limitations of PARP inhibitor therapy by identifying ways to increase DNA damage in tumor cells. Because these tumor cells have a defective DNA repair pathway, this increased accumulation of damage will make them hypersensitive to PARP inhibitors, resulting in faster killing that can prevent the emergence of resistance.
In this project, Dr. Verma will investigate damage to the nitrogen bases, the building blocks of DNA. She also aims to uncover modifications to the genome that increase DNA damage. Identifying these pathways will uncover therapeutic targets that can work together with PARP inhibitors to achieve rapid killing of cancer cells. In addition to improving the efficacy of PARP inhibitors, this work has the potential to outline a framework for predicting the patients who will benefit from such therapies.