The role of farnesyltransferase inhibitors in lung cancer therapy.
Protein farnesylation is required for the localization and function of several proteins pivotal to signal transduction pathways and cytoskeletal organization, including the Ras proteins. Ras proteins are constitutively activated in 30% of human tumors, including lung cancer tumors, as a consequence of mutations in ras genes. Farnesyltransferase inhibitors (FTIs) were thus designed to curtail the Ras-mediated aberrant signals that regulate cell proliferation, apoptosis, invasion, and angiogenesis. These processes are vital to the perpetuation of the malignant phenotype. However, current evidence suggests that the antitumor activity of FTIs is Ras-independent. This article reviews preclinical and clinical data pertinent to the use of FTIs in lung cancer.
Dy
Grace K
GK
Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Adjei
Alex A
AA