Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 20 July 2004
Vol. 2004, Issue 242, p. tw263
[DOI: 10.1126/stke.2422004TW263]


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.

N. P. Shah, C. Tran, F. Y. Lee, P. Chen, D. Norris, C. L. Sawyers, Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 305, 399-401 (2004). [Abstract] [Full Text]

Citation: Gleevec: The Sequel. Sci. STKE 2004, tw263 (2004).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882