Drugging Undruggable Molecular Cancer Targets

Annu Rev Pharmacol Toxicol. 2016;56:23-40. doi: 10.1146/annurev-pharmtox-010715-103440. Epub 2015 Nov 2.


Cancer, more than any other human disease, now has a surfeit of potential molecular targets poised for therapeutic exploitation. Currently, a number of attractive and validated cancer targets remain outside of the reach of pharmacological regulation. Some have been described as undruggable, at least by traditional strategies. In this article, we outline the basis for the undruggable moniker, propose a reclassification of these targets as undrugged, and highlight three general classes of this imposing group as exemplars with some attendant strategies currently being explored to reclassify them. Expanding the spectrum of disease-relevant targets to pharmacological manipulation is central to reducing cancer morbidity and mortality.

Keywords: RAS; cancer drug targets; oncogenes; phosphatases; transcription factors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*


  • Antineoplastic Agents