Sci. STKE, 20 July 2004
CANCER Gleevec: The Sequel
The tyrosine kinase inhibitor imatinib (Gleevec) is now a frontline treatment for chronic myelogenous leukemia (CML). As with most cancer therapies, however, a subset of patients develop resistance to imatinib, a problem that has been traced to the acquisition of specific mutations in the oncogenic BCR-ABL kinase targeted by the drug. Guided by these mutational data as well as crystallographic data detailing how imatinib binds to the ABL kinase domain, Shah et al. have isolated a new tyrosine kinase inhibitor that appears to have all of the favorable characteristics of imatinib--and more. Preclinical studies of this second-generation drug (an orally available thiazolecarboxamide) in a mouse model and in cultured bone marrow cells from CML patients indicate that it is more potent than imatinib and, importantly, retains activity against the majority of imatinib-resistant BCR-ABL mutants without significant toxicity.
Citation: Gleevec: The Sequel. Sci. STKE 2004, tw263 (2004).
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