TY - JOUR
T1 - Clinical activity of farnesyl transferase inhibitors in hematologic malignancies
T2 - Possible mecahnisms of action
AU - Jabbour, Elias
AU - Kantarjian, Hagop
AU - Cortes, Jorge
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
KW - Farnesyl transferase inhibitors
KW - Leukemia
KW - Ras pathway
KW - Signal transduction
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U2 - 10.1080/10428190412331272677
DO - 10.1080/10428190412331272677
M3 - Review article
C2 - 15512806
AN - SCOPUS:8644219632
SN - 1042-8194
VL - 45
SP - 2187
EP - 2195
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 11
ER -