Antimitotic drugs in cancer chemotherapy: promises and pitfalls

Biochem Pharmacol. 2013 Sep 15;86(6):703-10. doi: 10.1016/j.bcp.2013.07.010. Epub 2013 Jul 22.

Abstract

Cancer cells usually display higher proliferation rates than normal cells. Some currently used antitumor drugs, such as vinca alkaloids and taxanes, act by targeting microtubules and inhibiting mitosis. In the last years, different mitotic regulators have been proposed as drug target candidates for antitumor therapies. In particular, inhibitors of Cdks, Chks, Aurora kinase and Polo-like kinase have been synthesized and evaluated in vitro and in animal models and some of them have reached clinical trials. However, to date, none of these inhibitors has been still approved for use in chemotherapy regimes. We will discuss here the most recent preclinical information on those new antimitotic drugs, as well as the possible molecular bases underlying their lack of clinical efficiency. Also, advances in the identification of other mitosis-related targets will be also summarized.

Keywords: Cancer; Chemotherapy; Mitosis.

Publication types

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

MeSH terms

  • Antimitotic Agents / pharmacology*
  • Antineoplastic Agents / pharmacology
  • Benzamides / pharmacology
  • Clinical Trials as Topic
  • Cyclin-Dependent Kinases / antagonists & inhibitors*
  • Cyclin-Dependent Kinases / metabolism
  • Humans
  • Microtubules / drug effects
  • Mitosis / drug effects
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / metabolism
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Pyrimidinones
  • Quinazolines / pharmacology

Substances

  • Antimitotic Agents
  • Antineoplastic Agents
  • Benzamides
  • Neoplasm Proteins
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Pyrimidinones
  • Quinazolines
  • ispinesib
  • Protein Serine-Threonine Kinases
  • Cyclin-Dependent Kinases
  • adavosertib