Resensitization to Crizotinib by the Lorlatinib ALK Resistance Mutation L1198F

A resistance mutation (C1156Y) developed in a woman with anaplastic lymphoma kinase ( ALK )-rearranged lung cancer who had a response to crizotinib. She then acquired resistance to lorlatinib. A lorlatinib resistance mutation (L1198F) led to resensitization to crizotinib. Small-molecule tyrosine kin...

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Veröffentlicht in:The New England journal of medicine 2016-01, Vol.374 (1), p.54-61
Hauptverfasser: Shaw, Alice T, Friboulet, Luc, Leshchiner, Ignaty, Gainor, Justin F, Bergqvist, Simon, Brooun, Alexei, Burke, Benjamin J, Deng, Ya-Li, Liu, Wei, Dardaei, Leila, Frias, Rosa L, Schultz, Kate R, Logan, Jennifer, James, Leonard P, Smeal, Tod, Timofeevski, Sergei, Katayama, Ryohei, Iafrate, A. John, Le, Long, McTigue, Michele, Getz, Gad, Johnson, Ted W, Engelman, Jeffrey A
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Sprache:eng
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Zusammenfassung:A resistance mutation (C1156Y) developed in a woman with anaplastic lymphoma kinase ( ALK )-rearranged lung cancer who had a response to crizotinib. She then acquired resistance to lorlatinib. A lorlatinib resistance mutation (L1198F) led to resensitization to crizotinib. Small-molecule tyrosine kinase inhibitors are standard therapies for several types of cancer, including chronic myeloid leukemia, 1 epidermal growth factor receptor ( EGFR )–mutated non–small-cell lung cancer (NSCLC), 2 , 3 and ALK -rearranged NSCLC. 4 Although these therapies can be highly effective, resistance often develops. In patients whose disease relapses while they are receiving first-generation inhibitors, treatment with more potent and selective next-generation inhibitors can frequently reinduce durable responses. 5 – 9 The success of next-generation inhibitors in overcoming resistance has led to the common clinical practice of sequential treatment with increasingly potent and selective targeted therapies. In NSCLC, ALK rearrangement identifies a subgroup of . . .
ISSN:0028-4793
1533-4406
DOI:10.1056/NEJMoa1508887