Microtubule-Targeting Agents: Strategies To Hijack the Cytoskeleton

Trends Cell Biol. 2018 Oct;28(10):776-792. doi: 10.1016/j.tcb.2018.05.001. Epub 2018 Jun 2.


Microtubule-targeting agents (MTAs) such as paclitaxel and the vinca alkaloids are among the most important medical weapons available to combat cancer. MTAs interfere with intracellular transport, inhibit eukaryotic cell proliferation, and promote cell death by suppressing microtubule dynamics. Recent advances in the structural analysis of MTAs have enabled the extensive characterization of their interactions with microtubules and their building block tubulin. We review here our current knowledge on the molecular mechanisms used by MTAs to hijack the microtubule cytoskeleton, and discuss dual inhibitors that target both kinases and microtubules. We further formulate some outstanding questions related to MTA structural biology and present possible routes for future investigations of this fascinating class of antimitotic agents.

Keywords: microtubule-targeting agents; molecular mechanisms of action; tubulin-ligand binding modes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antimitotic Agents / chemistry
  • Antimitotic Agents / pharmacology*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Humans
  • Microtubules / drug effects*
  • Mitosis / drug effects*
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacology*
  • Phosphotransferases / antagonists & inhibitors*
  • Phosphotransferases / metabolism


  • Antimitotic Agents
  • Antineoplastic Agents, Phytogenic
  • Phosphotransferases
  • Paclitaxel