Role of farnesyltransferase inhibitors in hematologic malignancies.
The treatment of hematologic malignancies has progressed in the last few years. Identification of new pathways and target molecules in leukemia has ushered in a promising new era of therapy. Ras mutations have recently been implicated in the pathogenesis of acute leukemia, and inhibition of Ras signaling through the use of farnesyltransferase inhibitors (FTIs) has shown promise in early trials in acute myeloid leukemia (AML). Responses have not correlated with the presence of Ras mutations, suggesting that novel pathways are involved. In several early trials, FTIs have shown activity as single agents in poor-risk AML, suggesting a potential role in combination with standard chemotherapy. FTIs are now being tested in other clinical settings, such as myelodysplasia, chronic myelogenous leukemia and multiple myeloma, with encouraging preliminary activity.
Division of Hematology/Oncology, University of Miami, Sylvester Comprehensive Cancer Center, D8-4, Miami, FL 33136, USA. edgardo_ny@hotmail.com
Edgardo S
ES
Santos
Joseph D
JD
Rosenblatt
Mark
M
Goodman
D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009154:Mutation; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D018631:ras Proteins