MET overexpression

P3, N=412, Active, not recruiting, Hutchison Medipharma Limited | Trial completion date: Aug 2026 --> May 2028 | Trial primary completion date: Aug 2026 --> May 2028

These results indicate c-Met protein overexpression can be assessed before or after treatment since most patients maintain consistent c-Met status. As targeted therapies may elevate c-Met overexpression over time, retesting may be necessary in those with an oncogenic driver alteration initially diagnosed as c-Met negative.

Moreover, comprehensive in vitro and in vivo experiments demonstrate that nitidine significantly inhibits tumor progression through an LRPPRC-MET-G4-dependent mechanism. Collectively, our study suggests an epigenetic regulatory mechanism involving LRPPRC-MET-G4-mediated MET upregulation and provides a promising therapeutic strategy for MET-driven tumors using molecular glues that target the LRPPRC-MET-G4 interface.

The AMPK-FOXO1-CALB2 axis mediates MET-induced mitochondrial dysfunction and apoptosis, providing a mechanistic basis for MET to overcome progesterone resistance in ECC.

Given the importance of plasma membrane-associated MET in initiating its canonical signaling cascades, as well as the demonstrated non-canonical signaling from nuclear localized MET in different tumor cell types and in response to various environmental stimuli, we developed assay capability to measure levels of pY1235MET and total MET within the plasma membrane or nucleus; these assays enable future explorations of the biological and clinical relevance of MET subcellular localization patterns. Finally, using tissue microarrays of over 50 resected tumor specimens from patients with colorectal carcinoma or non-small cell lung cancer, we demonstrated that tumor levels of pY1235MET do not always track total MET expression, suggesting that measurement of activated MET in tumor could hold potential as an independent biomarker to identify additional patients who might benefit from MET-directed targeted therapy-beyond those with tumor MET amplification, MET overexpression, or established MET-activating mutations.

Vebreltinib plus an EGFR-TKI demonstrates favorable efficacy and manageable safety in real-world NSCLC patients with MET-driven resistance, with notable intracranial activity. Immunohistochemistry 3 + may serve as a practical predictive biomarker.

While accelerated approval underscores its therapeutic promise, long-term positioning will depend on confirmatory trials, refinement of biomarker testing, and optimization of patient selection. If validated, this strategy may redefine later-line treatment expectations by aligning cytotoxic payload delivery with biologically enriched disease subsets.

P1, N=18, Not yet recruiting, Peking Union Medical College Hospital

P2, N=19, Not yet recruiting, Shanghai Chest Hospital

P1/2, N=140, Recruiting, Chong Kun Dang Pharmaceutical | Not yet recruiting --> Recruiting

P=N/A, N=166, Ethics Committee of Cancer Hospital of Shandong First Medical University; Cancer Hospital of Shandong First Medical University

P2, N=37, Zhongshan Hospital, Fudan University; Zhongshan Hospital, Fudan University