{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:51:19Z","timestamp":1790351479829,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2011,7,5]],"date-time":"2011-07-05T00:00:00Z","timestamp":1309824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2012,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The use of tyrosine kinase inhibitors (TKIs) has become an integral component of cancer therapy. Imatinib mesylate, a breakpoint cluster region\u2010Abelson <jats:italic>BCR\u2010ABL1<\/jats:italic> inhibitor, was the first TKI approved in cancer medicine and has served as a model for the development of similar agents for other cancers. An important drawback of TKI therapy is the development of resistance, frequently through the acquisition of mutations. Mutations at the gatekeeper residues of <jats:italic>BCR\u2010ABL1<\/jats:italic> (eg, the threonine\u2010to\u2010isoleucine mutation at codon 315) and other oncogenic kinases have proven highly resistant to currently available TKIs. Advances in the structural biology of oncogenic kinases have facilitated the rational development of TKIs that are active against gatekeeper mutations. Cancer 2011;. \u00a9 2011 American Cancer Society.<\/jats:p>","DOI":"10.1002\/cncr.26225","type":"journal-article","created":{"date-parts":[[2011,7,5]],"date-time":"2011-07-05T12:26:37Z","timestamp":1309868797000},"page":"293-299","source":"Crossref","is-referenced-by-count":93,"title":["The rise and fall of gatekeeper mutations? 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