Targeting protein prenylation for cancer therapy

Norbert Berndt, Andrew D. Hamilton, Saïd M. Sebti

Research output: Contribution to journalReview articlepeer-review

Abstract

Protein farnesylation and geranylgeranylation, together referred to as prenylation, are lipid post-translational modifications that are required for the transforming activity of many oncogenic proteins, including some RAS family members. This observation prompted the development of inhibitors of farnesyltransferase (FT) and geranylgeranyltransferase 1 (GGT1) as potential anticancer drugs. In this Review, we discuss the mechanisms by which FT and GGT1 inhibitors (FTIs and GGTIs, respectively) affect signal transduction pathways, cell cycle progression, proliferation and cell survival. In contrast to their preclinical efficacy, only a small subset of patients responds to FTIs. Identifying tumours that depend on farnesylation for survival remains a challenge, and strategies to overcome this are discussed. One GGTI has recently entered the clinic, and the safety and efficacy of GGTIs await results from clinical trials.

Original languageEnglish (US)
Pages (from-to)775-791
Number of pages17
JournalNature Reviews Cancer
Volume11
Issue number11
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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