Reference Detail

Ref Type Journal Article
PMID (27343442)
Authors Heist RS, Sequist LV, Borger D, Gainor JF, Arellano RS, Le LP, Dias-Santagata D, Clark JW, Engelman JA, Shaw AT, Iafrate AJ
Title Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping.
Journal Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Vol 11
Issue 8
Date 2016 Aug
URL
Abstract Text MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping is a targetable alteration in lung cancer. Treatment with MET proto-oncogene, receptor tyrosine kinase inhibitor can cause dramatic responses in patients whose cancers have MET exon 14 skipping. Little is known, however, about acquired resistance in patients with MET exon 14 skipping.Biopsy specimens obtained at baseline and at the time of progression for a patient being treated with crizotinib were compared using targeted next-generation sequencing to assess for mechanisms of resistance.An acquired mutation in the MET kinase domain, D1228N, was found at time of progression on crizotinib in a patient with MET exon 14 skipping.One potential mechanism of acquired resistance to crizotinib in patients with MET exon 14 skipping is through second-site mutations in the MET gene. Understanding mechanisms of resistance will be important in optimizing therapy in these patients.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MET del exon14 MET D1228N lung squamous cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical case study, a patient with squamous cell lung cancer harboring a MET exon 14 skipping mutation was determined to have acquired MET D1228N after progression on Xalkori (crizotinib) therapy (PMID: 27343442). 27343442