Targeting Cdc42 in cancer

Expert Opin Ther Targets. 2013 Nov;17(11):1263-73. doi: 10.1517/14728222.2013.828037. Epub 2013 Aug 19.

Abstract

Introduction: The Rho GTPases are a family of proteins that control fundamental cellular processes in response to extracellular stimuli and internal programs. Rho GTPases function as molecular switches in which the GTP-bound proteins are active and GDP-bound proteins are inactive. This article will focus on one Rho family member, Cdc42, which is overexpressed in a number of human cancers, and which might provide new therapeutic targets in malignancies.

Areas covered: In this article, the key regulators and effectors of Cdc42 and their molecular alterations are described. The complex interactions between the signaling cascades regulated by Cdc42 are also analyzed.

Expert opinion: While mutations in Cdc42 have not been reported in human cancer, aberrant expression of Cdc42 has been reported in a variety of tumor types and in some instances has been correlated with poor prognosis. Recently, it has been shown that Cdc42 activation by oncogenic Ras is crucial for Ras-mediated tumorigenesis, suggesting that targeting Cdc42 or its effectors might be useful in tumors harboring activating Ras mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Transformation, Neoplastic
  • Humans
  • Neoplasms / metabolism*
  • Signal Transduction / drug effects
  • cdc42 GTP-Binding Protein / drug effects*
  • cdc42 GTP-Binding Protein / metabolism
  • rho GTP-Binding Proteins / metabolism

Substances

  • Antineoplastic Agents
  • cdc42 GTP-Binding Protein
  • rho GTP-Binding Proteins