title: Farnesyltransferase inhibitors.
abstract: The targeting of molecular abnormalities in neoplasms may provide an opportunity to improve the selectivity of cancer therapy. Ras mutations are a common genetic event in human cancers. Other genetic changes in tumors can signal through ras-dependent pathways as well. The targeting of ras through the inhibition of Ras protein farnesylation is one new cancer treatment strategy under clinical evaluation. Several farnesyltransferase inhibitors (FTIs) have been evaluated in phase I trials. The toxicity and maximally tolerated doses of several FTIs have been determined, and clinical trials are underway to evaluate FTIs in combination with conventional cytotoxic chemotherapy agents. Also underway are attempts to develop assays to measure the biological effects of the FTI in patients. Inhibition of farnesylation of a number of surrogate markers are currently being investigated. These efforts may provide insight into the mechanism of action of these compounds and lead to improved patient selection for clinical trials.
authors.affiliation: Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA 19104-4283, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Hahn
authors.forename: E
authors.initials: E
authors.lastname: Bernhard
authors.forename: W G
authors.initials: WG
authors.lastname: McKenna
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051231:Farnesyltranstransferase; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use; D018631:ras Proteins / Q000037:antagonists & inhibitors*; 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; C425231:L 778,123; 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