Development of farnesyltransferase inhibitors for clinical cancer therapy: focus on hematologic malignancies.
Farnesyltransferase inhibitors (FTIs) target and inhibit the peptide prenylating enzyme farnesyltransferase. This new class of signal transduction inhibitors is being tested clinically in diverse malignancies, with encouraging results in hematololgic malignancies and breast cancer in particuarl. Critical questions have yet to be answered, for example, optimal dose and schedule, disease subgroups most likely to respond, and appropriate combinations with standard cytotoxics and new biologics. Gene profiling studies of malignant target cells obtained during FTI clinical trials will help to identify patients who are likely to respond to FTIs and to develop mechanisms for overcoming FTI resistance. Clinical trials and correlative laboratory studies in progress and under development will define the optimal roles of FTIs in cancer patients.
Karp
Judith E
JE
Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231, USA. jkarp2@jhmi.edu
Lancet
Jeffrey E
JE
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase