Cytotoxicity of paclitaxel in breast cancer is due to chromosome missegregation on multipolar spindles.

ABSTRACT: The blockbuster chemotherapy drug paclitaxel is widely presumed to cause cell death in tumors as a consequence of mitotic arrest, as it does at concentrations routinely used in cell culture. However, we determine here that paclitaxel levels in primary breast tumors are well below those required to elicit sustained mitotic arrest. Instead, cells in these lower concentrations of drug proceed through mitosis without substantial delay and divide their chromosomes on multipolar spindles, resulting in chromosome missegregation and cell death. Consistent with these cell culture data, most mitotic cells in primary human breast cancers contain multipolar spindles after paclitaxel treatment. Contrary to the previous hypothesis, we find that mitotic arrest is dispensable for tumor regression in patie

SUBMITTER: Zasadil LM 

PROVIDER: S-EPMC4176609 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature