Interphase microtubules: chief casualties in the war on cancer?

Angela Ogden1, Padmashree C G Rida1, Michelle D Reid2

  • 1Department of Biology, Georgia State University, Atlanta, GA 30303, USA.

Drug Discovery Today
|November 9, 2013
PubMed

Insights

Microtubule-targeting agents (MTAs) impact interphase cells, not just mitosis. This challenges the traditional view and explains their effectiveness in cancer chemotherapy.

Area of Science:

  • Oncology
  • Cell Biology
  • Pharmacology

Background:

  • Microtubule-targeting agents (MTAs) are primarily understood to act during mitosis.
  • This view is challenged by evidence of MTA effects on interphase cellular processes.
  • Clinical observations, like low mitotic cell counts in tumors, contradict the traditional model.

Purpose of the Study:

  • To re-evaluate the mechanistic basis of MTA action.
  • To investigate the significance of interphase activities in MTA efficacy.
  • To reconcile the clinical success of MTAs with their limited mitotic effects.

Main Methods:

  • Review of existing literature on MTA mechanisms.
  • Analysis of clinical data correlating MTA efficacy with tumor proliferation.
  • Examination of cellular processes affected by MTAs in interphase.

Main Results:

  • MTAs significantly impact various interphase cellular functions, including axonal transport, transcription, translation, mitochondrial permeability, immune cell function, directional cell migration, and centrosome clustering.
  • The efficacy of MTAs does not correlate with tumor proliferation rates.
  • Many targeted antimitotic drugs have shown limited clinical success.

Conclusions:

  • MTAs exert significant mitosis-independent effects.
  • The primary mode of action for MTAs in chemotherapy likely involves interphase activities.
  • A paradigm shift is needed to understand MTA mechanisms, focusing on their interphase effects.

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