Targeting DNA damage repair precision medicine strategies in cancer
Juliette Brownlie, Sanat Kulkarni, Mashael Algethami, Jennie Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan
Abstract
DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as platinum sensitive epithelial ovarian cancers. However, lessons learnt from the clinical use of PARP inhibitors also confirm that not all patients respond either due to intrinsic or acquired resistance. Therefore, the search for additional synthetic lethality approaches is an active area of translational and clinical research. Here, we review the current clinical state of PARP inhibitors and other evolving DNA repair targets including ATM, ATR, WEE1 inhibitors and others in cancer.