An overview of farnesyltransferase inhibitors and their role in lung cancer therapy.

Protein farnesylation is required for the localization and function of several proteins pivotal to signal transduction pathways and cytoskeletal organization, among which are the ras proteins. Mutations in one family member K-ras occur in 50% of non-small cell lung cancer and have been associated with poor prognosis. Because the ability of ras to induce malignant transformation depends on its plasma membrane localization, farnesyltransferase inhibitors (FTIs) were designed to curtail ras-mediated aberrant signals, which stimulate cell proliferation, apoptosis, invasion, and angiogenesis. However, current evidence suggests that the antitumor activity of FTIs may be ras-independent. This article reviews preclinical and clinical data pertinent to the use of FTIs in lung cancer.