{"doi":"10.1016/j.jtocrr.2020.100133","title":"Differential Pattern of Resistance and Sensitivity to Different Classes of MET Inhibitors for MET-Amplified Tumors With MET-D1228X or MET-Y1230X Mutations","abstract":"We thank Drs. Fujino and Mitsudomi1Fujino T. Mitsudomi T. Acquired resistance mechanism for MET-TKI.JTO Clin Res Rep. 2021; 2: 100134Abstract Full Text Full Text PDF Google Scholar for their interest in our description of MET mutations as a mechanism of resistance to dual EGFR-MET inhibition in EGFR-mutated plus MET-amplified lung cancer.2Piper-Vallillo A.J. Halbert B.T. Rangachari D. Kobayashi S.S. Costa D.B. Acquired resistance to osimertinib plus savolitinib is mediated by MET-D1228 and MET-Y1230 mutations in EGFR-mutated MET-amplified lung cancer.JTO Clin res rep. 2020; 1: 100071Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar The ongoing approvals and late-stage development of multiple type I MET tyrosine kinase inhibitors—such as capmatinib, tepotinib, savolitinib, and crizotinib—have paved the way for the use of these therapies in the clinical care of patients with tumors driven by MET aberrations.1Fujino T. Mitsudomi T. Acquired resistance mechanism for MET-TKI.JTO Clin Res Rep. 2021; 2: 100134Abstract Full Text Full Text PDF Google Scholar,3Wolf J. Seto T. Han J.Y. et al.Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer.N Engl J Med. 2020; 383: 944-957Crossref PubMed Scopus (130) Google Scholar, 4Paik P.K. Felip E. Veillon et al.Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations.N Engl J Med. 2020; 383: 931-943Crossref PubMed Scopus (132) Google Scholar, 5Drilon A. Clark J.W. Weiss J. et al.Antitumor activity of crizotinib in lung cancers harboring a MET exon 14 alteration.Nat Med. 2020; 26: 47-51Crossref PubMed Scopus (113) Google Scholar However, the widespread use of type I MET inhibitors will also highlight the inherited vulnerability of tumor adaptation mediated by on-target resistance through MET kinase domain mutations, including MET-D1228X and MET-Y1230X mutations.2Piper-Vallillo A.J. Halbert B.T. Rangachari D. Kobayashi S.S. Costa D.B. Acquired resistance to osimertinib plus savolitinib is mediated by MET-D1228 and MET-Y1230 mutations in EGFR-mutated MET-amplified lung cancer.JTO Clin res rep. 2020; 1: 100071Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Some type II MET inhibitors (i.e., cabozantinib, merestinib, and glesatinib) have preclinical activity against MET-amplified tumors co-harboring MET-D1228X or MET-Y1230X mutations.1Fujino T. Mitsudomi T. Acquired resistance mechanism for MET-TKI.JTO Clin Res Rep. 2021; 2: 100134Abstract Full Text Full Text PDF Google Scholar,2Piper-Vallillo A.J. Halbert B.T. Rangachari D. Kobayashi S.S. Costa D.B. Acquired resistance to osimertinib plus savolitinib is mediated by MET-D1228 and MET-Y1230 mutations in EGFR-mutated MET-amplified lung cancer.JTO Clin res rep. 2020; 1: 100071Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Fujino and Mitusudomi1Fujino T. Mitsudomi T. Acquired resistance mechanism for MET-TKI.JTO Clin Res Rep. 2021; 2: 100134Abstract Full Text Full Text PDF Google Scholar eloquently highlighted the preclinical differences in the inhibitory profiles of these two mutations and pointed toward the need for the development of more potent MET inhibitors with an enhanced pattern of activity against MET kinase domain mutations. This work was funded in part through National Institutes of Health / National Cancer Institute grants R37 CA218707 (to Dr. Costa). Acquired Resistance Mechanism for MET Tyrosine Kinase InhibitorJTO Clinical and Research ReportsVol. 2Issue 3PreviewWe read with great interest the article entitled “Acquired resistance to osimertinib plus savolitinib is mediated by MET D1228 and Y1230 mutations in EGFR-mutated, MET-amplified lung cancer” by Piper-Vallillo et al.1 recently published in JTO Clinical and Research Reports. In this article, the authors postulated that MET D1228N/Y/H and Y1230C secondary mutations could be the mechanisms of acquired resistance to type I MET inhibitor, savolitinib, along with EGFR tyrosine kinase inhibitor","journal":"JTO Clinical and Research Reports","year":2021,"id":223543,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":297162,"name":"Susumu Kobayashi","orcid":"0000-0003-2262-4001","position":1,"is_corresponding":false},{"id":297163,"name":"Daniel B. 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