MET amplification

P=N/A, N=55, Not yet recruiting, Fuzhou University Affiliated Provincial Hospital; Fuzhou University Affiliated Provincial Hospital

This deep learning model demonstrated excellent performance in multi-omics subtype predictions. In, conclusion, this study systematically elucidates the molecular heterogeneity of LUAD through a multi-omics integration strategy, establishes a clinically relevant molecular classification system, and provides a theoretical foundation for developing personalized treatment plans for LUAD.

By sharing the diagnosis and treatment process of this patient and reviewing the relevant literature, we aim to help clinicians enhance their understanding of two rare diseases, namely pleomorphic RMS and sarcomatoid carcinoma of the liver.

Encouragingly, several MET TKIs such as capmatinib, tepotinib, and savolitinib have been approved for the treatment of MET exon 14 skipping mutations. On 14 May 2025, the U.S. Food and Drug Administration granted accelerated approval to telisotuzumab vedotin-tllv for adult patients with locally advanced or metastatic non-squamous NSCLC whose tumors exhibit high c-Met protein overexpression and who have already received prior systemic therapy. In this review, we summarize the structure and physiological role of the MET receptor, the molecular mechanisms underlying aberrant MET activation, its contribution to acquired resistance against targeted therapies, and emerging strategies for effectively targeting MET alterations in NSCLC.

P2, N=47, Active, not recruiting, AstraZeneca | Trial completion date: Aug 2025 --> Jan 2027 | Trial primary completion date: Aug 2025 --> Jan 2027

P2, N=25, Recruiting, Jeeyun Lee | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

Crizotinib demonstrated clinical activity across tumors with METamp and METex14.Subprotocol C1, but not C2, met its primary endpoint. In METex14 disease, a read count cutoff >50,000 may help distinguish true pathogenic variants from low-level splice transcripts and enable more accurate classification.

After resolution with corticosteroids, treatment was switched to afatinib. This study highlights the heterogeneous approaches to OILI and the potential feasibility of rechallenge in selected patients. Given the expanding osimertinib use for early and advanced stage NSCLC, further research is warranted to refine treatment decisions and optimize patient safety.

The savolitinib-osimertinib combination improved PFS versus chemotherapy in patients with EGFR mutation-positive, MET-amplified NSCLC that had progressed on EGFR TKI therapy, while maintaining a favourable tolerability profile. This regimen offers a potential oral treatment option for this biomarker-selected population.

Prevalence of secondary RET mutations after SRIs was low, underscoring greater role for off-target resistance. Recurrent acquired alterations involving tumor suppressor genes or upstream regulators of MAPK and PI3K pathways were identified, most commonly MET amplification. Continued efforts to characterize SRI resistance biology are critical to guide development of novel therapeutic strategies.

Treatment-related adverse events of grade 3 or higher occurred in 2 patients (8.7%) in cohort 1 and 12 patients (57.1%) in cohort 2. Osimertinib plus savolitinib showed promising antitumor activity and manageable safety.

Our study demonstrated that the biological and clinical significance of MET alterations is highly context dependent. In lung cancer, MET serves primarily as a predictive biomarker for targeted therapy, whereas in brain tumors, it functions as a prognostic marker of genomic instability and aggressive disease. These findings advocate for context-specific clinical management strategies.