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 |
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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 . . . |
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ISSN: | 0028-4793 1533-4406 |
DOI: | 10.1056/NEJMoa1508887 |