Targeting the process of farynesylation for therapy of hematologic malignancies.
In sum, the FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies. We are just beginning to explore and elucidate the mechanisms by which transformed cells respond to FTIs and the optimal settings in which they do so. The clinical trials that are currently in progress and under development will provide the critical foundations for defining the optimal roles of FTIs in patients with AML and other hematologic disorders. The correlative laboratory studies to define the mechanisms by which FTIs alter cellular metabolism and modulate the activities of specific signaling pathways in both normal and malignant marrow precursors are a pivotal part of this effort. What we learn about FTIs in the clinic and the laboratory will apply broadly to the effective and safe application of all signal transduction inhibitors.
Karp
Judith E
JE
The Sidney Kimmel Cancer Center at Johns Hopkins, 1650 Orleans St., Bunting-Blaustein Cancer Research Bldg., Room 289, Baltimore, Maryland 21231-1000, USA. jkarp2@jhmi.edu
Lancet
Jeffrey E
JE
D002986:Clinical Trials as Topic; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D017368:Protein Prenylation / Q000187:drug effects*
D051231:Farnesyltranstransferase; D010770:Phosphotransferases