BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer.

ABSTRACT: TP53 wild-type breast tumors rarely undergo a complete pathological response after chemotherapy treatment. These patients have an extremely poor survival rate and studies show these tumors preferentially undergo senescence instead of apoptosis. These senescent cells persist after chemotherapy and secrete cytokines and chemokines comprising the senescence associated secretory phenotype, which promotes survival, proliferation, and metastasis. We hypothesized that eliminating senescent tumor cells would improve chemotherapy response and extend survival. Previous studies have shown "senolytic" agents selectively kill senescent normal cells, but their efficacy in killing chemotherapy-induced senescent cancer cells is unknown. We show that ABT-263, a BH3 mimetic that targets antiapoptotic protei

SUBMITTER: Shahbandi A 

PROVIDER: S-EPMC7560696 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature