Evolving roles of MET as a therapeutic target in NSCLC and beyond
Cet article met en évidence les raisons qui justifient le ciblage des altérations du gène MET dans divers types de tumeurs solides et passe en revue les résultats cliniques d'anticancéreux émergeants ciblant ces altérations et approuvés par la "U.S. Food and Drug Administration" (inhibiteurs de tyrosine kinase, anticorps monoclonaux ou bispécifiques et conjugués anticorps-médicament)
Alterations in the proto-oncogene MET are associated with tumour development, invasion and metastasis across various solid cancers. Therapeutically actionable MET alterations include MET exon 14 skipping (METex14) mutations, MET amplification and/or MET overexpression and MET fusions, which vary in incidence by tumour type. In contrast to rare de novo MET alterations, acquired MET amplification and/or MET overexpression is a relatively common phenomenon that is associated with distinct clinical implications and responses to treatment. METex14 is a distinct oncogenic driver mutation in non-small-cell lung cancer (NSCLC). To date, the MET tyrosine-kinase inhibitors (TKIs) capmatinib, tepotinib and savolitinib have been approved for the treatment of advanced-stage METex14-mutant NSCLC. However, the treatment paradigms for MET-altered solid tumours are rapidly evolving to include diverse MET-targeted agents. Emerging data support the role of MET TKIs, anti-MET antibodies and MET-directed antibody–drug conjugates (ADCs) as monotherapy or in combination with other therapies for NSCLC or other tumour types with MET amplification and/or overexpression. Indeed, in May 2025, the MET-directed ADC telisotuzumab vedotin was approved by the FDA for patients with previously treated advanced-stage nonsquamous NSCLC overexpressing MET (≥50% of tumour cells with 3+ staining on immunohistochemistry). Understanding the unique MET-related adverse events will be crucial when incorporating these agents into daily clinical practice. In this Review, we highlight the rationale for targeting MET alterations across various solid tumour types and provide a summary of the clinical efficacy and toxicity profiles of the approved and emerging MET-targeted TKIs, monoclonal or bispecific antibodies and ADCs.
Nature Reviews Clinical Oncology , résumé, 2025