Targeting Bcl-xL to eliminate chemotherapy-induced tumor dormancy and prevent breast cancer metastasis.

ABSTRACT: Chemotherapy-induced tumor dormancy is a major barrier to curative cancer therapy, particularly in triple-negative breast cancer (TNBC), where dormant residual cells evade treatment and fuel late relapses. To define survival mechanisms sustaining dormancy, we examined four breast cancer models: HER2-positive murine MMC and human SK-BR-3, and TNBC murine 4T1 and human MDA-MB-231. Dormancy was induced with low-dose FAC (5-Fluorouracil, Adriamycin, Cyclophosphamide). Across all models, dormant cells maintained high Bcl-xL expression. shRNA knockdown of Bcl-xL increased chemotherapy-induced apoptosis and prevented relapse in vitro and in vivo. Pharmacologic inhibition with A-1331852 improved chemotherapy, particularly in TNBC, and transient dosing avoided compensatory Survivin induction. Syste

SUBMITTER: Gupta K 

PROVIDER: S-EPMC12859104 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature