Ras farnesyltransferase inhibition: a novel and safe approach for cancer chemotherapy

The 21-kDa Ras proteins are well known for their regulatory role in oncogenic, mitogenic, and developmental signaling pathways. GTP activated Ras interacts directly with the Raf protein to recruit the MAP kinases and their subordinates. Attachment of Ras protein to the plasma membrane that requires farnesylation by farnesyl pyrophosphate at its C-terminus, is essential for its biological activity. Ras oncogenes are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. A promising pharmacological approach of antagonizing oncogenic Ras activity is to develop inhibitors of farnesyl transferase. These inhibitors may be useful in blocking the action of Ras onco-proteins.