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Searching for the elusive targets of farnesyltransferase inhibitors

Nature Reviews Cancer volume 3, pages 945–951 (2003)Cite this article

Abstract

Farnesyltransferase (FTase) inhibitors (FTIs) were developed originally as anti-RAS compounds and novel target-based drugs for cancer treatment. The analyses of FTIs continue in the clinic, but the antitumour activity cannot be ascribed simply to inhibition of RAS. Although FTI action is due to inhibition of FTase, and RAS proteins are indeed substrates for this enzyme, the RAS proteins that are most frequently mutated in human cancers escape FTI inhibition. RHOB has been suggested as a target, but is this issue resolved or do the crucial targets of FTIs remain to be identified?

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Figure 1: RAS processing and association with the plasma membrane.
Figure 2: Farnesyltransferase inhibitors (FTIs) inhibit FTase modification of RAS and other proteins.
Figure 3: FTIs target the PI3K–AKT survival pathway to induce apoptosis.
Figure 4: Expected properties of farnesylated proteins involved in FTI-induced growth inhibition.
Figure 5: Small GTPase candidate targets of FTIs.

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Author information

Authors and Affiliations

  1. the Department of Oncology, Drug Discovery Program, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, Tampa, 33612, Florida, USA

    Saïd M. Sebti

  2. the Department of Pharmacology, University of North Carolina, Chapel Hill, 27599, North Carolina, USA

    Channing J. Der

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  1. Saïd M. Sebti
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The authors declare no competing financial interests.

Related links

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DATABASES

LocusLink

AKT2

APAF1

ARHI/NOEY2

BAD

BCL-XL

CDC42

CDKN2A

CENPE

CENPF

DBC2

ERBB1

ERBB2

HRAS

KRAS

NRAS

p53

PRL1

PRL2

PRL3

PTEN

RAC1

RAL

RAP

RERG

RHEB

RIG

RND3

TSC2

OMIM

tuberous sclerosis syndrome

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Sebti, S., Der, C. Searching for the elusive targets of farnesyltransferase inhibitors. Nat Rev Cancer 3, 945–951 (2003). https://doi.org/10.1038/nrc1234

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