Clinical activity of farnesyl transferase inhibitors in hematologic malignancies: Possible mecahnisms of action

Elias Jabbour, Hagop Kantarjian, Jorge Cortes

Research output: Contribution to journalReview article

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2187-2195
Number of pages9
JournalLeukemia and Lymphoma
Volume45
Issue number11
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

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Keywords

  • Farnesyl transferase inhibitors
  • Leukemia
  • Ras pathway
  • Signal transduction

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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