Farnesyltransferase inhibitors: Novel compounds in development for the treatment of myeloid malignancies

Jorge E. Cortes, Razelle Kurzrock, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

The farnesyltransferase inhibitors (FTIs) have been shown in early clinical trials to elicit antitumor actions in a broad range of solid and hematologic malignancies. The mechanism of FTI action involves blockade of farnesyltransferase, an enzyme implicated in multiple cell-signaling pathways involved in proliferation, angiogenesis, or decreased apoptosis. Of the four main classes of FTIs, two orally bioavailable FTIs have advanced farthest in clinical development. ZARNESTRA™ (formerly R115777, Ortho Biotech Oncology, Raritan, NJ) and Sarasar (formerly SCH66336, Schering-Plough, Kenilworth, NJ) have demonstrated biologic and clinical activity in a range of solid tumors, and Zarnestra phase I trials have documented clinical responses in approximately 30% of patients with high-risk leukemias or myelodysplastic syndrome (MDS). The main across-class toxicities associated with the use of FTIs are myelosuppression and fatigue. Certain toxicities, such as the QTc abnormalities associated with L-778,123, do not appear to be class related. As results of phase II trials with FTIs in acute and chronic myeloid leukemias and in MDS become available, clinicians will learn more about the potential role of this class of targeted anticancer drugs-and possibly about the clinical distinctions among members of this class.

Original languageEnglish (US)
Pages (from-to)26-30
Number of pages5
JournalSeminars in Hematology
Volume39
Issue number3 SUPPL. 2
DOIs
StatePublished - Jul 2002
Externally publishedYes

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Farnesyltranstransferase
tipifarnib
Neoplasms
Myelodysplastic Syndromes
Therapeutics
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Acute Myeloid Leukemia
Fatigue
Leukemia
Clinical Trials
Apoptosis
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Hematology

Cite this

Farnesyltransferase inhibitors : Novel compounds in development for the treatment of myeloid malignancies. / Cortes, Jorge E.; Kurzrock, Razelle; Kantarjian, Hagop M.

In: Seminars in Hematology, Vol. 39, No. 3 SUPPL. 2, 07.2002, p. 26-30.

Research output: Contribution to journalArticle

Cortes, Jorge E. ; Kurzrock, Razelle ; Kantarjian, Hagop M. / Farnesyltransferase inhibitors : Novel compounds in development for the treatment of myeloid malignancies. In: Seminars in Hematology. 2002 ; Vol. 39, No. 3 SUPPL. 2. pp. 26-30.
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