Mitosis-targeting therapies: a troubleshooting guide

Curr Opin Pharmacol. 2013 Aug;13(4):519-28. doi: 10.1016/j.coph.2013.03.011. Epub 2013 Apr 12.

Abstract

Several mitotic kinases and kinesins are currently considered as cancer targets based on their critical role during the cell division cycle and their significant level of expression in human tumors. Yet, their use is limited by the lack of selectivity against tumor cells, the low percentage of mitotic cells in many human tumors, and dose-limiting side-effects. As a consequence, initial clinical trials have shown limited responses. Despite these drawbacks, inhibiting mitosis is a promising strategy that deserves further development. Future advances will benefit from more specific inhibitors with better pharmacodynamic properties, a clear physiological characterization and cell-type-specific requirements of old and new mitotic targets, and rational strategies based on synthetic lethal interactions to improve selectivity against tumor cells.

Publication types

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

MeSH terms

  • Animals
  • Antimitotic Agents / pharmacology
  • Antimitotic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Humans
  • Kinesin / antagonists & inhibitors
  • Kinesin / metabolism
  • Mitosis / drug effects*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinases / metabolism

Substances

  • Antimitotic Agents
  • Protein Kinase Inhibitors
  • Protein Kinases
  • Kinesin