[Expert Consensus on Targeted Therapy of NSCLC with MET Exon 14 
Skipping Mutation]

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Context:

• The MET exon 14 skipping mutation arises from the loss of the c-Cbl tyrosine binding site.
• This alteration disrupts proteasomal degradation of MET proteins, leading to pathway activation and potential tumorigenesis.
• It occurs in 0.9%–4.0% of non-small cell lung cancer (NSCLC) cases.

Purpose:

• To provide expert consensus and clinical guidance on the targeted therapy of NSCLC with MET exon 14 skipping mutations.
• To standardize clinical practices for Chinese physicians managing these specific NSCLC cases.
• To highlight the importance of identifying MET exon 14 skipping mutations for treatment selection.

Summary:

• MET exon 14 skipping mutations in NSCLC result from c-Cbl binding site loss, causing MET protein stabilization and oncogenic signaling.
• Patients with advanced NSCLC harboring this mutation are candidates for MET inhibitor therapy.
• MET inhibitors demonstrate high response rates and favorable safety, prolonging survival in affected patients.

Impact:

• This consensus aims to optimize the use of MET inhibitors in NSCLC patients with exon 14 skipping mutations.
• Standardized guidance can improve treatment outcomes and survival for this patient subgroup.
• Facilitates evidence-based clinical decision-making for targeted therapy in NSCLC.