Targeting MET amplification in Gastro-oesophageal (GO) malignancies and overcoming MET inhibitor resistance: challenges and opportunities.

A standardized definition of MET positivity is critical to enhance patient selection. Early successes targeting the METex14 skipping mutation demonstrate the potent therapeutic effects of METi in a clearly molecularly defined cohort. There is robust preclinical rationale and early-phase data supporting exploitation of immune system interaction with MET. Pragmatic investigation of rational therapeutic combinations based on molecular profiling of both primary and metastatic disease sites with sequential circulating tumor DNA analysis can inform successful clinical development of METi agents in GOC.