Immunohistochemical Assays of Farnesyltransferase Inhibition in Patient Samples

As a result of early reports indicating that farnesylation was required for maturation of Ras proteins, there has been extensive interest in farnesyl-transferase (FT) as a potential target of antineoplastic therapy (1 –3 ). At the present time, three different FT inhibitors (FTIs), SCH66336, R115777, and BMS-214662, are undergoing clinical testing. Phase III studies with R115777 in pancreatic and colorectal cancer have completed accrual. Because the FTIs are among the first potential anticancer drugs that inhibit aberrantly activated signal transduction pathways in neoplastic cells, there is considerable interest in assessing their cellular effects in the clinical setting. A variety of assays have been proposed for this purpose.