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Circumventing Resistance to Kinase-Inhibitor Therapy
In a recent issue of the New England Journal Of Medicine, Brian Drucker, inventor of the powerful cancer drug Gleevec, offers a fascinating overview of recent efforts to, as it were, reverse engineer Gleevec in order to design new drugs to more effectively combat cancers that have become Gleevec-resistant. He also offers his thoughts as to why pharmaceutical companies have remained focused this small group of patients who have failed on the standard therapy.
These drugs were developed rapidly. A driving factor was the high quality of the basic science associated with clinical trials in CML. Mechanisms of relapse were rapidly identified, and the solution to the crystal structure of ABL in complex with [Gleevec] prompted rapid modification of the structure of the drug. Only a continued investment in a basic understanding of disease mechanisms will make possible similar advances.
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