Is there a future for prenyltransferase inhibitors in cancer therapy?

Abstract

It has been over 20 years since it was first recognized that the function of both normal and oncogenic Ras is dependent on the post-translational modification termed farnesylation. Since that time, intense effort has been expended on the development of farnesyltransferase inhibitors as novel anticancer agents. Over 70 clinical trials have now been conducted, with limited efficacy demonstrated. Here we provide an update of the most recently published clinical trials, discuss the use of the RASGRP1/APTX two-gene expression screen to select patients with acute myeloid leukemia for therapy, and report on the latest discoveries related to the targets of prenyltransferase inhibitors.

• Authors: Sarah A Holstein, Raymond J Hohl
• Journal: Current opinion in pharmacology (Curr Opin Pharmacol) Vol. 12 Issue 6 Pg. 704-9 (Dec 2012) ISSN: 1471-4973 [Electronic] England
• PMID: 22817869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• APTX protein, human
• Antineoplastic Agents
• DNA-Binding Proteins
• Enzyme Inhibitors
• Guanine Nucleotide Exchange Factors
• Nuclear Proteins
• RASGRP1 protein, human
• Dimethylallyltranstransferase

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• DNA-Binding Proteins (genetics)
• Dimethylallyltranstransferase (antagonists & inhibitors, metabolism)
• Drug Design
• Enzyme Inhibitors (pharmacology)
• Genes, ras
• Guanine Nucleotide Exchange Factors (genetics)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, genetics, pathology)
• Neoplasms (drug therapy, enzymology, pathology)
• Nuclear Proteins (genetics)
• Protein Prenylation
• Protein Processing, Post-Translational