K-ras as a target for cancer therapy

Bret B. Friday, Alex Adjei

Research output: Contribution to journalReview article

182 Scopus citations

Abstract

The central role K-, H- and N-Ras play in regulating diverse cellular pathways important for cell growth, differentiation and survival is well established. Dysregulation of Ras proteins by activating mutations, overexpression or upstream activation is common in human tumors. Of the Ras proteins, K-ras is the most frequently mutated and is therefore an attractive target for cancer therapy. The complexity of K-ras signaling presents many opportunities for therapeutic targeting. A number of different approaches aimed at abrogating K-ras activity have been explored in clinical trials. Several of the therapeutic agents tested have demonstrated clinical activity, supporting ongoing development of K-ras targeted therapies. However, many of the agents currently being evaluated have multiple targets and their antitumor effects may not be due to K-Ras inhibition. To date, no selective, specific inhibitor of K-ras is available for routine clinical use. In this review, we will summarize the structure and function of K-ras with attention to its role in tumorigenesis and discuss the successes and failures of the various strategies designed to therapeutically target this important oncogene.

Original languageEnglish (US)
Pages (from-to)127-144
Number of pages18
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1756
Issue number2
DOIs
StatePublished - Nov 25 2005

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Keywords

  • Cancer therapy
  • Clinical trial
  • K-ras
  • Oncogene
  • Ras effector

ASJC Scopus subject areas

  • Biophysics
  • Cancer Research
  • Oncology

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