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


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.


CONCLUSIONS
The interphase actions of MTAs are critical to the full spectrum of their effects in cancer cells, even in cell culture models.
Department of Pharmacology and Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, U.S.A.
April L
AL
Risinger
Department of Pharmacology and Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, U.S.A.
Nicholas F
NF
Dybdal-Hargreaves
Department of Pharmacology and Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, U.S.A. Mooberry@uthscsa.edu.
Susan L
SL
Mooberry
D050256:Antimitotic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D050257:Tubulin Modulators / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D050256:Antimitotic Agents; D050257:Tubulin Modulators
Microtubule; docetaxel; eribulin; ixabepilone; microtubule destabilizer; paclitaxel; vinorelbine