Paclitaxel-induced mitotic arrest results in a convergence of apoptotic dependencies that can be safely exploited by BCL-X_L degradation to overcome cancer chemoresistance.

ABSTRACT: Paclitaxel and other microtubule-targeting agents are cornerstone therapies for diverse cancers, including lung, breast, cervical, pancreatic, and ovarian malignancies. Paclitaxel induces tumor cell apoptosis during mitosis by disrupting microtubule dynamics required for chromosome segregation. However, despite initial responsiveness, many tumors develop resistance, limiting therapeutic durability. Here, we used high-grade serous ovarian carcinoma (HGSOC), the most common and lethal subtype of ovarian cancer, as a model to dissect the mechanisms underlying this resistance. We find that paclitaxel-induced mitotic arrest triggers degradation of the pro-survival protein MCL-1 and upregulation of BCL-XL, followed by inactivating phosphorylation of BCL-XL at Ser62 to promote apoptosis. In resis

SUBMITTER: Qin X 

PROVIDER: S-EPMC12262480 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature