Chromosomal instability sensitizes patient breast tumors to multipolar divisions induced by paclitaxel.

ABSTRACT: Paclitaxel (Taxol) is a cornerstone of cancer treatment. However, its mechanism of cytotoxicity is incompletely understood and not all patients benefit from treatment. We show that patients with breast cancer did not accumulate sufficient intratumoral paclitaxel to induce mitotic arrest in tumor cells. Instead, clinically relevant concentrations induced multipolar mitotic spindle formation. However, the extent of early multipolarity did not predict patient response. Whereas multipolar divisions frequently led to cell death, multipolar spindles focused into bipolar spindles before division at variable frequency, and maintaining multipolarity throughout mitosis was critical to induce the high rates of chromosomal instability necessary for paclitaxel to elicit cell death. Increasing multipola

SUBMITTER: Scribano CM 

PROVIDER: S-EPMC8612166 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature