Treatment status of non-small cell lung cancer with METexon14 skipping mutation / 国际肿瘤学杂志

MET exon14 (METex14) skipping mutation is an independent driver gene in non-small cell lung cancer (NSCLC) . About 3%-4% of NSCLC patients carry METex14 skipping mutation. These patients have poor prognoses and poor responses to traditional chemotherapy and immunotherapy. Highly selective MET inhibitors such as capmatinib, tepotinib, savolitinib have shown good efficacy and safety data in clinical trials, which bring new treatment options for patients with METex14 skipping mutations.

Expert Consensus on Targeted Therapy of NSCLC with MET Exon 14 Skipping Mutation / 中国肺癌杂志

The mesenchymal-epithelial transition factor (MET) exon 14 skipping mutation is mainly caused by the loss of c-Cbl tyrosine binding site. This mutation could result in a decrease in the degradation rate of proteasome-mediated MET proteins, trigger continuous activation of downstream pathways, and ultimately lead to tumorigenesis. The incidence of MET exon 14 skipping mutation in patients with non-small cell lung cancer (NSCLC) is 0.9% to 4.0%. Patients with advanced NSCLC are recommended to test MET exon 14 skipping mutations who may benefit from MET inhibitors-targeted therapy. MET inhibitors have a high objective response rate and good safety profiles, which could prolong the survival of NSCLC patients with MET exon 14 skipping mutations. The Lung Cancer Specialty Committee of Chinese Elderly Health Care Association organized multidisciplinary experts to give suggestions on the important issues of clinical aspects for targeted therapy of MET exon 14 skipping mutation in NSCLC according to the clinical practice experiences and evidences based medicine. "Expert Consensus on Targeted Therapy of NSCLC with MET Exon 14 Skipping Mutation" is proposed, aiming to provide standardized guidances for the clinical practice of Chinese physicians.
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MET14 exon skipping mutation and non-small cell lung cancer / 国际肿瘤学杂志

The molecular mechanism of the skipping mutation of MET14 exon (METex14) is mainly that the skipping of METex14 leads to the loss of the c-Cbl tyrosine binding site, which causes the proteasome-mediated degradation of MET protein to decrease, which continuously activates the MET signal, and finally leads to tumorigenesis. The incidence of METex14 skipping mutations in non-small cell lung cancer is 3%-4%. Drugs that act on skipping mutations of METex14 include crizotinib, capmatinib, tepotinib, savolitinib, and have a high objective remission rate and good safety. However, due to gene amplification, second site mutations, bypass activation and pathological type conversion, drug resistance after targeted drug therapy requires attention.