Lung Cancer with exon 14 Skipping Mutation: Genetic Feature, Current Treatments, and Future Challenges.

exon 14 skipping mutation (∆ex14) is present about 3% of non-small cell lung cancers (NSCLCs). NSCLC patients with ∆ex14 are characterized by an average age of over 70 years at diagnosis, a smoking history and a higher frequency in pleomorphic carcinoma and adenosquamous cell carcinoma than in adenocarcinoma. It has also been reported that NSCLCs with ∆ex14 often have codriver alterations such as amplification (6-28%), alterations (5-17%), alterations (8%), alterations (21%), or mutation/amplification (~14%). In 2020, the approval of two MET-tyrosine kinase inhibitors (TKIs), capmatinib and tepotinib, for NSCLCs carrying ∆ex14 dawned a new era for MET-targeted therapy. These drugs yielded progression-free survival of 5.4-12.4 months in clinical trials; however, it has also been reported that one-third to half of patients show inherent resistance to MET-TKIs. In addition, the emergence of acquired resistance to MET-TKIs is inevitable. In this review, we summarize the clinical and molecular characteristics of NSCLCs with ∆ex14, the efficacy and safety of capmatinib and tepotinib, the inherent and acquired resistance mechanisms to MET-TKIs, and new treatment strategies for NSCLCs with ∆ex14 in the near future.