Breast cancer cell lines exhibit differential sensitivities to microtubule-targeting drugs independent of doubling time

April L Risinger, Nicholas F. Dybdal-Hargreaves, Susan L Mooberry

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)5845-5850
Number of pages6
JournalAnticancer Research
Volume35
Issue number11
StatePublished - Nov 1 2015

Fingerprint

Drug Delivery Systems
Microtubules
Breast Neoplasms
Cell Line
Interphase
Cell Culture Techniques
Pharmaceutical Preparations
Neoplasms
Therapeutics

Keywords

  • Docetaxel
  • Eribulin
  • Ixabepilone
  • Microtubule
  • Microtubule destabilize
  • Paclitaxel
  • Vinorelbine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Breast cancer cell lines exhibit differential sensitivities to microtubule-targeting drugs independent of doubling time. / Risinger, April L; Dybdal-Hargreaves, Nicholas F.; Mooberry, Susan L.

In: Anticancer Research, Vol. 35, No. 11, 01.11.2015, p. 5845-5850.

Research output: Contribution to journalArticle

@article{381b72db3c494683b0d2728887783976,
title = "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.",
keywords = "Docetaxel, Eribulin, Ixabepilone, Microtubule, Microtubule destabilize, Paclitaxel, Vinorelbine",
author = "Risinger, {April L} and Dybdal-Hargreaves, {Nicholas F.} and Mooberry, {Susan L}",
year = "2015",
month = "11",
day = "1",
language = "English (US)",
volume = "35",
pages = "5845--5850",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "11",

}

TY - JOUR

T1 - Breast cancer cell lines exhibit differential sensitivities to microtubule-targeting drugs independent of doubling time

AU - Risinger, April L

AU - Dybdal-Hargreaves, Nicholas F.

AU - Mooberry, Susan L

PY - 2015/11/1

Y1 - 2015/11/1

N2 - 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.

AB - 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.

KW - Docetaxel

KW - Eribulin

KW - Ixabepilone

KW - Microtubule

KW - Microtubule destabilize

KW - Paclitaxel

KW - Vinorelbine

UR - http://www.scopus.com/inward/record.url?scp=84946070830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946070830&partnerID=8YFLogxK

M3 - Article

C2 - 26504006

AN - SCOPUS:84946070830

VL - 35

SP - 5845

EP - 5850

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 11

ER -