title: Clinical activity of farnesyl transferase inhibitors in hematologic malignancies: possible mechanisms of action.
abstract: Farnesyl transferase inhibitors (FTIs) are a novel class of anti-cancer agents that competitively inhibit farnesyl protein transferase (FTase). Initially developed to inhibit the prenylation necessary for Ras activation, their mechanism of action seems to be more complex, involving other proteins unrelated to Ras. FTIs have been developed and tested across a wide range of human cancers. At least 3 agents within this family have been investigated in hematologic malignancies. These are tipifarnib (R115777, Zarnestra), lonafarnib (SCH66336, Sarasar), both of which are orally administered, and BMS-214662, which is given intravenously. Preliminary results from clinical trials demonstrate enzyme target inhibition, a favorable toxicity profile and promising efficacy. Ongoing studies will better determine their mechanism of action and the role of combination with other agents, defining their place in the therapeutic arsenal of hematologic disorders.
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism; D003986:Dibenzocycloheptenes
chemical_list: D019883:Alkyl and Aryl Transferases; D000970:Antineoplastic Agents; D001569:Benzodiazepines; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D007093:Imidazoles; D010880:Piperidines; D011725:Pyridines; D015363:Quinolones; D018631:ras Proteins; C115354:lonafarnib; D003986:Dibenzocycloheptenes; C415151:7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine; C402769:tipifarnib