Normally, Gleevec slips into a narrow, wedgelike cleft in the center of Bcr-abl—like “an arrow pierced through the center of the protein’s heart,”1032 as one chemist described it. Gleevec-resistant mutations in Bcr-abl change the molecular “heart” of the Bcr-abl protein so that the drug can no longer access the critical cleft in the protein, thus rendering the drug ineffective. In Mayfield’s case, a single alteration in the Bcr-abl protein had rendered it fully resistant to Gleevec, resulting in the sudden relapse of leukemia. To escape targeted therapy, cancer had changed the target. To
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