Perspectives on farnesyl transferase inhibitors in cancer therapy.
The discovery that the transforming activity of oncogenic Ras depends upon its post-translational farnesylation has led to the development of farnesyl transferase inhibitors (FTIs). FTIs inhibit the growth of ras-transformed cells in vitro and induce tumor regression in Ras-dependent tumors. Currently, FTIs are undergoing clinical trials in various solid or hematological malignancies. In this review, we will summarize our current knowledge on cellular effect and molecular mechanism of FTIs. We will then describe recent clinical trials and propose some clues for their interpretation. Based on pre-clinical findings, we will emphasize on the optimal use of FTIs in anti-cancer strategy and lastly, we will insist on the interest of combining FTIs with chemotherapy, radiotherapy or other targeted agents.
Mazieres
Julien
J
Département Innovation Thérapeutique et Oncologie Moléculaire, INSERM U563, Institut Claudius Regaud, 20-24, rue du pont Saint-Pierre, Toulouse cedex 31052, France.
Pradines
Anne
A
Favre
Gilles
G
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D051231:Farnesyltranstransferase; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase