Targeting RAD51-Mediated Homologous Recombination as a Treatment for Advanced Solid and Hematologic Malignancies: Opportunities and Challenges Ahead.

Abstract

RAD51 is integral in homologous recombination DNA damage repair and has garnered much interest as both a biomarker and potential therapeutic target in oncology. Multiple in vitro and in vivo studies have demonstrated its role as a predictive marker, particularly in the context of platinum-based therapies and poly ADP-ribose polymerase (PARP) inhibitors. In this review, we highlight the development of RAD51 inhibitors, with a focus on novel molecules and ongoing clinical trials. Despite many efforts to develop effective and tolerable direct RAD51 inhibitors, identification of these agents remains challenging. Clinically, however, there may be a role of pharmacological indirect RAD51 inhibition.