title: Farnesyltransferase inhibitors: where are we now?
abstract: BACKGROUND
  Farnesyltransferase inhibitors (FTIs) target multiple pathways implicated in the pathogenesis of solid and hematologic malignancies.
  
  
  METHODS
  Novel preclinical and clinical data on FTIs.
  
  
  RESULTS
  Results of clinical trials of FTIs are critically summarized: Phase I - II studies demonstrated that tipifarnib (the most extensively investigated FTI) had antileukemic activity. The rates of complete response (CR), partial response (PR) and/or CR with incomplete platelet recovery (CRp) in patients with MDS and refractory/poor-risk AML were 5 - 25% and 11 - 14%, respectively (hematological improvement, 17 - 35% and 8 - 9.5%, respectively). A Phase III study comparing tipifarnib with best supportive care, including hydroxyurea in patients with untreated AML ≥ 70 years old showed no survival benefit in the tipifarnib arm. A two-gene classifier (RASGRP1:APTX gene expression ratio) predicted response and survival, indicating that a two-gene expression assay may help select patients with AML who would benefit from tipifarnib.
  
  
  CONCLUSIONS
  Patient selection should become a priority for targeted agent drug development. Clinical trials selecting patients who would benefit from FTIs should be designed to define the role of FTIs in the treatment of hematological malignancies and solid tumors.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Investigational Cancer Therapeutics, 1515 Holcombe Blvd., Unit 455, Houston 77030, USA.
authors.forename: Apostolia Maria
authors.initials: AM
authors.lastname: Tsimberidou
authors.forename: Chandtip
authors.initials: C
authors.lastname: Chandhasin
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011905:Genes, ras / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D015363:Quinolones; D051231:Farnesyltranstransferase; C402769:tipifarnib