RB loss sensitizes triple-negative breast cancer to apoptosis induced by cellular stress.

ABSTRACT: Functional loss of RB1 is a common genetic alteration in triple-negative breast cancer (TNBC) and is associated with poor response to targeted therapies, including CDK4/6 inhibitors. In this study, we perform an unbiased drug screen and identify that co-targeting distinct cell cycle processes such as DNA repair and mitosis induce synthetic lethality selectively in RB-deficient models. While RB loss promotes replication stress and mitotic dysregulation, the selective lethality observed with these combinations arises from an alternate mechanism. Under RB-deficient conditions, cells undergo rapid apoptosis in response to cellular stress induced by cell cycle inhibition. This pro-apoptotic response is further augmented by using a pharmacological agent, birinapant that targets XIAP, which is an

SUBMITTER: Witkiewicz AK 

PROVIDER: S-EPMC12644999 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature