The potential of farnesyltransferase inhibitors as cancer chemotherapeutics.

Abstract:

:Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational modification, farnesylation, which is required for the subcellular localization of Ras to the plasma membrane and is critical to Ras cell-transforming activity. Inhibitors of the enzyme that catalyzes Ras farnesylation, farnesyl-protein transferase (FPTase), have been developed. These compounds inhibit the tumorigenic phenotypes of ras-transformed cells and human tumor cells in cell culture and in animal models. Moreover, FPTase inhibitors have not demonstrated toxicity to normal cells in culture or to normal tissues in mice. FPTase inhibitors are among the first small molecule compounds designed from studies of oncogenes that might serve as novel cancer chemotherapeutics.

authors

Gibbs JB,Oliff A

doi

10.1146/annurev.pharmtox.37.1.143

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

143-66

eissn

0362-1642

issn

1545-4304

journal_volume

37

pub_type

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