Targeting the acidic tumor microenvironment to improve PARP inhibitor efficacy in ovarian cancer

Project summary

Resistance to PARP inhibitors, such as Olaparib, presents a critical challenge in managing epithelial ovarian cancer (EOC). My research indicates that this resistance may arise due to an acidic tumor microenvironment. I’ve found that targeting the epigenetic regulator p300 protein can effectively counteract this resistance induced by the acidic tumor microenvironment. My study aims to develop a novel combinatory therapeutic strategy by integrating a p300 inhibitor, IACS16559, with a PARP inhibitor, olaparib. This approach seeks to improve efficacy and/or overcome resistance to PARP inhibitors in EOCs with homologous recombination deficiency such as those caused by BRCA mutations.

This grant was made possible in part by generous donations from George and Paulette Collias in memory of Matina, Georgiana and Cindy Gatziolis; and the Mike and Patti Hennessy Foundation.