{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:52:55Z","timestamp":1787032375846,"version":"build-2736575974"},"reference-count":46,"publisher":"Harborside Press, LLC","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    EGFR tyrosine kinase inhibitors (TKIs) have significantly improved clinical outcomes for patients with non\u2013small cell lung cancer (NSCLC) harboring EGFR-activating mutations. However, resistance to TKI therapy often develops due to secondary\n                    <jats:italic>EGFR<\/jats:italic>\n                    mutations or the activation of bypass signalling pathways. Next-generation sequencing (NGS) can efficiently identify actionable genetic alterations throughout treatment.\n                    <jats:italic>MET<\/jats:italic>\n                    amplification is a well-established off-target resistance mechanism. Additionally, rarer mechanisms, such as\n                    <jats:italic>NTRK1<\/jats:italic>\n                    gene fusions, have been reported. This report highlights a case of a 58-year-old male diagnosed with bone-metastatic NSCLC harboring the\n                    <jats:italic>EGFR<\/jats:italic>\n                    L858R mutation. After receiving dacomitinib and almonertinib sequentially, plasma-based NGS revealed the emergence of\n                    <jats:italic>EGFR<\/jats:italic>\n                    T790M-trans-C797S mutations, prompting a switch to a combination therapy of almonertinib and gefitinib. Upon disease progression, repeat NGS identified\n                    <jats:italic>EGFR<\/jats:italic>\n                    T790M-cis&amp;trans-C797S mutations and a novel\n                    <jats:italic>POT1<\/jats:italic>\n                    ::\n                    <jats:italic>NTRK3<\/jats:italic>\n                    fusion in the blood. The fusion retained a complete NTRK kinase domain without frameshift variants, making it a target for treatment. Larotrectinib was incorporated into the dual EGFR-TKI regimen, forming a triplet therapy. Although this resulted in grade 3 dermatitis, the condition resolved after discontinuing gefitinib. At multiorgan progression, matched tissue- and plasma-based NGS identified\n                    <jats:italic>MET<\/jats:italic>\n                    amplification. Subsequently, the patient was started on a triple-inhibition regimen targeting EGFR, NTRK, and MET, which achieved a partial response with favorable tolerability. This is the first reported case of a novel, targetable\n                    <jats:italic>POT1<\/jats:italic>\n                    ::\n                    <jats:italic>NTRK3<\/jats:italic>\n                    fusion as a potential off-target mechanism mediating EGFR-TKI resistance, occurring alongside\n                    <jats:italic>MET<\/jats:italic>\n                    amplification in a patient with NSCLC harboring acquired\n                    <jats:italic>EGFR<\/jats:italic>\n                    L858R\/T790M\/C797S mutations. Concomitant inhibition of EGFR, NTRK, and MET was safe and resulted in a significant response, underscoring the importance of precision medicine guided by matched NGS.\n                  <\/jats:p>","DOI":"10.6004\/jnccn.2024.7070","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T09:55:16Z","timestamp":1735293316000},"source":"Crossref","is-referenced-by-count":5,"title":["Response to EGFR\/NTRK\/MET Co-Inhibition Guided by Paired NGS in Advanced NSCLC With Acquired EGFR L858R\/T790M\/C797S Mutations"],"prefix":"10.6004","volume":"23","author":[{"given":"Xue","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Shao","sequence":"additional","affiliation":[{"name":"Genecast Biotechnology Co., Ltd., Wuxi, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"},{"name":"Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Xue","sequence":"additional","affiliation":[{"name":"Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"},{"name":"Laboratory of Clinical Cell Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Nat Rev Cancer","first-page":"169","article-title":"Epidermal growth factor receptor mutations in lung cancer","volume":"7","author":"Sharma SV","year":"2007","unstructured":"Sharma SV, Bell DW, Settleman J,  Epidermal growth factor receptor mutations in lung cancer. 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