Farnesyl transferase inhibitors in myeloid disorders

Farnesyl transferase inhibitors (FTIs), a novel class of anticancer agents that competitively inhibit farnesyl protein transferase, are currently being developed and tested across a wide range of human cancers. Myeloid malignancies are reasonable disease targets in that they likely overexpress relevant biologic targets, such as Ras, mitogen-activated protein kinase (MAPK), or AKT. Several phase I clinical trials using FTIs in myeloid malignancies have been performed, demonstrating enzyme target inhibition, low toxicity, and anticancer activity. Many phase II trials are now under way, aiming to assess the response rate and to identify the actual downstream signal transduction targets that may be modified by these agents. It is expected that results from these trials will optimize the role of FTIs in patients with myeloid disor-ders by identifying patient and disease characteristics that will predict for response, facilitating their incorporation into current therapeutic strategies and providing insight into effective methods of combining FTIs with other antineoplastics.