Breast Cancer Cell Lines Exhibit Differential Sensitivities to Microtubule-targeting Drugs Independent of Doubling Time.

Abstract

BACKGROUND: Microtubule-targeting agents (MTAs) are a mainstay in breast cancer treatment, yet patient responses differ. The underlying mechanisms of these differences are unknown. While MTAs are mitotic inhibitors, recent evidence highlights that non-mitotic effects of these drugs can contribute to their anticancer effects. It is critical to identify the non-mitotic mechanisms that could contribute to differences among MTAs. However, it is not clear whether rapidly dividing cells in culture are optimal tools to address these mechanistic questions in interphase cells. MATERIALS AND METHODS: Detailed concentration response curves for five MTAs in a panel of diverse breast cancer cell lines were generated. RESULTS: Substantial differences among both drugs and cell lines, consistent with the clinical scenario, were observed. Importantly, these differences do not correlate with cell doubling time. CONCLUSION: The interphase actions of MTAs are critical to the full spectrum of their effects in cancer cells, even in cell culture models.