TY - JOUR
T1 - Clinical activity of tipifarnib in hematologic malignancies
AU - Jabbour, Elias
AU - Kantarjian, Hagop
AU - Cortes, Jorges
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2007/3
Y1 - 2007/3
N2 - Farnesyltransferase inhibitors are a novel class of anticancer agents that competitively inhibit farnesyltransferase. Initially developed to inhibit the farnesylation that is necessary for Ras activation, their mechanism of action seems to be more complex, involving other proteins unrelated to Ras. Of the four classes of farnesyltransferase inhibitors, at least three agents have been investigated in hematologic malignancies. Tipifarnib (R-115777), an orally administered non-peptidomimetic farnesyltransferase inhibitor, has shown promising clinical activity. Preliminary results from clinical trials demonstrate enzyme target inhibition, an acceptable toxicity profile and promising evidence of clinical activity. Ongoing studies will better determine the mechanism of action of tipifarnib and the role of combination with other agents, defining its place in the therapeutic arsenal of hematologic disorders.
AB - Farnesyltransferase inhibitors are a novel class of anticancer agents that competitively inhibit farnesyltransferase. Initially developed to inhibit the farnesylation that is necessary for Ras activation, their mechanism of action seems to be more complex, involving other proteins unrelated to Ras. Of the four classes of farnesyltransferase inhibitors, at least three agents have been investigated in hematologic malignancies. Tipifarnib (R-115777), an orally administered non-peptidomimetic farnesyltransferase inhibitor, has shown promising clinical activity. Preliminary results from clinical trials demonstrate enzyme target inhibition, an acceptable toxicity profile and promising evidence of clinical activity. Ongoing studies will better determine the mechanism of action of tipifarnib and the role of combination with other agents, defining its place in the therapeutic arsenal of hematologic disorders.
KW - Farnesyltransferase inhibitors
KW - Leukemia
KW - Ras pathway
KW - Signal transduction
KW - Tipifarnib
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U2 - 10.1517/13543784.16.3.381
DO - 10.1517/13543784.16.3.381
M3 - Article
C2 - 17302532
AN - SCOPUS:33947171980
SN - 1354-3784
VL - 16
SP - 381
EP - 392
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 3
ER -