c-Met
c-Met, also known as the cellular mesenchymal–epithelial transition factor (c-MET), is a membrane protein and an established target in cancer research.
c-Met, also known as the cellular mesenchymal–epithelial transition factor (c-MET), is a membrane protein and an established target in cancer research. Its expression has been investigated as a tissue biomarker in colorectal cancer, oral squamous cell carcinoma, and early-stage classic Hodgkin lymphoma, although its prognostic value may vary by disease and clinical setting. Studies of oral squamous cell carcinoma have also examined spatial differences in c-MET expression between primary tumors and matched lymph-node metastases.
Therapeutic strategies directed against c-Met include small-molecule kinase inhibitors, aptamer–drug conjugates, antibody-based approaches, and aptamer-based ubiquitin-mediated protein degradation. Current drug-development work includes combinations or multitarget strategies involving EGFR, B7H3, STAT3, and VEGFR-2, with efforts focused on improving potency, tumor accumulation, payload release, and endosomal escape. These approaches are being evaluated in relation to apoptosis, cell-cycle control, proliferation, drug resistance, and antitumor activity in cancers including colorectal cancer and hepatocellular carcinoma.
Where the papers sit
11 papers from the last 6 months study c-Met directly · updated from PubMed 2 Nov 2026
Study type 2 clinical trials · 1 observational · 1 human data · 6 preclinical · 1 unclassified
Themes 3 themes · 1 new direction
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Bispecific and Aptamer Therapies
Bispecific EGFR/c-MET antibodies and c-MET-directed aptamer conjugates are moving toward selective delivery of cytotoxic payloads or degraders. In colorectal cancer, EMB-01 is being tested as a treatment for heavily pretreated metastatic disease. Aptamer studies emphasize rapid tumor accumulation, payload release, endosomal escape, and ubiquitin-mediated degradation. EGFR, c-MET, and B7H3 profiling supports biomarker selection, whereas c-MET immunohistochemistry lacked prognostic value in Hodgkin lymphoma.
5 papers · 45.5%
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c-Met Inhibitor Discovery
Structure-guided small-molecule design is expanding c-Met inhibitor activity while engaging apoptosis, cell-cycle control, and related kinases. Lead optimization uses indolin-2-one, isoindoline-1,3-dione, isatin, and thienopyrimidine scaffolds, with docking, potency, and cytotoxicity as recurring endpoints. Dual c-Met/STAT3 blockade and VEGFR-2 targeting aim to deepen antitumor effects, particularly in hepatocellular carcinoma models. Translation beyond in vitro activity remains open, including selectivity, pharmacology, and in vivo efficacy.
4 papers · 36.4%
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PD-L1 in Squamous Cancer
c-MET inhibition with tepotinib is linked to PD-L1 upregulation and immunosuppression-related changes in the esophageal squamous carcinoma microenvironment. Spatial heterogeneity of PD-L1 and c-MET in oral squamous cell carcinoma complicates biomarker assessment from single tumor samples. The recurring clinical question is whether c-MET inhibition may alter sensitivity to PD-1/PD-L1-directed treatment rather than act independently. Current evidence defines immune and spatial associations, but does not establish an optimal combination strategy.
2 papers · 18.2%
c-Met can serve as a tumor-cell delivery receptor for cytotoxic payloads rather than solely as a signaling target
The c-Met-targeting aptamer–drug conjugate in multiple c-Met-overexpressing tumor models used receptor-mediated internalization to deliver MMAE and produce cytotoxicity that was explicitly independent of MET mutation status, whereas the other studies chiefly treat c-Met as a signaling target, biomarker, or therapeutic-binding site. This reframes c-Met overexpression as an address for selective payload delivery, potentially extending treatment beyond tumors in which c-Met inhibition itself is effective 42679803Sep.
Papers
The 11 papers from the last 6 months that study c-Met directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
Bispecific and Aptamer Therapies (5)
- Optimizing Endosomal Escape for Effective Aptamer-Based Ubiquitin-Mediated Degradation of c-Met. ACS applied materials & interfaces · 18 Oct 2026 PMID 42891827
- Immunohistochemistry for c-MET, HLA class II, and CD68 does not show prognostic value in early-stage classic Hodgkin lymphoma patients in the EORTC-GELA H9 intergroup randomised trial. PloS one · 8 Oct 2026 PMID 42848781
- Profiling EGFR, c-MET, and B7H3 co-expression to guide next-generation dual-drug conjugate strategies in colorectal cancer. The journal of pathology. Clinical research · 30 Sept 2026 PMID 42811483
- Fast tumor accumulation and payload release of c-Met targeting aptamer-drug conjugate enables robust anti-tumor efficacy. Cell reports. Medicine · 1 Sept 2026 PMID 42679803
- EMB-01, an Anti-EGFR/c-MET Bispecific Antibody, in Patients with Heavily Pretreated Metastatic Colorectal Cancer from a Phase Ib/II, Open-Label, Multicenter Study. Clinical cancer research : an official journal of the American Association for Cancer Research · 24 Aug 2026 PMID 42635595
c-Met Inhibitor Discovery (4)
- Thieno[2,3-d]pyrimidine scaffold optimization for synergistic c-Met/STAT3 blockade: Synthesis, structure-activity relationships, in vitro potency, and apoptotic pathways in colorectal cancer. Bioorganic chemistry · 21 Sept 2026 PMID 42767173
- New indolin-2-one and isoindoline-1,3-dione derivatives as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro, in vivo, and in silico evaluation. Bioorganic chemistry · 13 Jul 2026 PMID 42442295
- Design, synthesis, and bioactivity assessment of highly potent isatin-based small-molecules bearing 3-hydrazineyl-6-aryl-1,2,4-triazine moieties as potential c-MET targeting anticancer agents. Bioorganic chemistry · 27 May 2026 PMID 42202586
- A novel c-Met inhibitor containing chiral pyrrolidine side chain and its application as anti-tumor agents. European journal of medicinal chemistry · 14 May 2026 PMID 42134160
PD-L1 in Squamous Cancer (2)
- c-MET Inhibition Is Accompanied by PD-L1 Upregulation and Immunosuppression-Related Tumor Microenvironment Changes in Esophageal Squamous Cell Carcinoma, With Enhanced Antitumor Activity in Combination With Anti-PD-1 Therapy. Cancer medicine · 1 Nov 2026 PMID 42968226
- Exploring spatial heterogeneity of PD-L1 and c-MET expression in oral squamous cell carcinoma. Oral and maxillofacial surgery · 16 Sept 2026 PMID 42747499
By study type
Clinical trials (2)
- Immunohistochemistry for c-MET, HLA class II, and CD68 does not show prognostic value in early-stage classic Hodgkin lymphoma patients in the EORTC-GELA H9 intergroup randomised trial. PloS one · 8 Oct 2026 PMID 42848781
- EMB-01, an Anti-EGFR/c-MET Bispecific Antibody, in Patients with Heavily Pretreated Metastatic Colorectal Cancer from a Phase Ib/II, Open-Label, Multicenter Study. Clinical cancer research : an official journal of the American Association for Cancer Research · 24 Aug 2026 PMID 42635595
Observational studies and case reports (1)
- Exploring spatial heterogeneity of PD-L1 and c-MET expression in oral squamous cell carcinoma. Oral and maxillofacial surgery · 16 Sept 2026 PMID 42747499
Human data, design not indexed (1)
- Profiling EGFR, c-MET, and B7H3 co-expression to guide next-generation dual-drug conjugate strategies in colorectal cancer. The journal of pathology. Clinical research · 30 Sept 2026 PMID 42811483
Preclinical: animal, cell and lab studies (6)
- c-MET Inhibition Is Accompanied by PD-L1 Upregulation and Immunosuppression-Related Tumor Microenvironment Changes in Esophageal Squamous Cell Carcinoma, With Enhanced Antitumor Activity in Combination With Anti-PD-1 Therapy. Cancer medicine · 1 Nov 2026 PMID 42968226
- Thieno[2,3-d]pyrimidine scaffold optimization for synergistic c-Met/STAT3 blockade: Synthesis, structure-activity relationships, in vitro potency, and apoptotic pathways in colorectal cancer. Bioorganic chemistry · 21 Sept 2026 PMID 42767173
- Fast tumor accumulation and payload release of c-Met targeting aptamer-drug conjugate enables robust anti-tumor efficacy. Cell reports. Medicine · 1 Sept 2026 PMID 42679803
- New indolin-2-one and isoindoline-1,3-dione derivatives as potential anti-hepatocellular carcinoma agents targeting VEGFR-2: Synthesis, in vitro, in vivo, and in silico evaluation. Bioorganic chemistry · 13 Jul 2026 PMID 42442295
- Design, synthesis, and bioactivity assessment of highly potent isatin-based small-molecules bearing 3-hydrazineyl-6-aryl-1,2,4-triazine moieties as potential c-MET targeting anticancer agents. Bioorganic chemistry · 27 May 2026 PMID 42202586
- A novel c-Met inhibitor containing chiral pyrrolidine side chain and its application as anti-tumor agents. European journal of medicinal chemistry · 14 May 2026 PMID 42134160
Unclassified: not yet indexed with MeSH (1)
- Optimizing Endosomal Escape for Effective Aptamer-Based Ubiquitin-Mediated Degradation of c-Met. ACS applied materials & interfaces · 18 Oct 2026 PMID 42891827
Written from 11 PubMed abstracts, each one listed by PMID above. Published: 2026-11-02. Drafted by language models from published abstracts; not medical advice.