Farnesyltransferase inhibitors in hematologic malignancies

New horizons in therapy

Jeffrey E. Lancet, Judith Karp

Research output: Contribution to journalArticle

Abstract

Farnesyltransferase inhibitors (FTIs) are small-molecule inhibitors that selectively inhibit farnesylation of a number of intracellular substrate proteins such as Ras. Preclinical work has revealed their ability to effectively inhibit tumor growth across a wide range of malignant phenotypes. Many hematologic malignancies appear to be reasonable disease targets, in that they express relevant biologic targets, such as Ras, mitogen-activated protein kinase (MAPK), AKT, and others that may depend on farnesyl protein transferase (FTase) activity to promote proliferation and survival. A host of phase I trials have been recently launched to assess the applicability of FTIs in hematologic malignancies, many of which demonstrate effective enzyme target inhibition, low toxicity, and some clinical responses. As a result, phase 2 trials have been initiated in a variety of hematologic malignancies and disease settings to further validate clinical activity and to identify down-stream signal transduction targets that may be modified by these agents. It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents.

Original languageEnglish (US)
Pages (from-to)3880-3889
Number of pages10
JournalBlood
Volume102
Issue number12
DOIs
StatePublished - Dec 1 2003

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Farnesyltranstransferase
Hematologic Neoplasms
Prenylation
Signal transduction
Hematologic Diseases
Therapeutics
Transferases
Mitogen-Activated Protein Kinases
Toxicity
Tumors
Signal Transduction
Proteins
Phenotype
Molecules
Survival
Substrates
Enzymes
Growth
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Farnesyltransferase inhibitors in hematologic malignancies : New horizons in therapy. / Lancet, Jeffrey E.; Karp, Judith.

In: Blood, Vol. 102, No. 12, 01.12.2003, p. 3880-3889.

Research output: Contribution to journalArticle

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