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    GENE:

    MET (MET proto-oncogene, receptor tyrosine kinase)

    i
    Other names: DFNB97, AUTS9, RCCP2, C-Met, HGFR, HGF Receptor, Met Proto-Oncogene, HGF/SF Receptor, Proto-Oncogene C-Met, Scatter Factor Receptor, Tyrosine-Protein Kinase Met, Hepatocyte Growth Factor Receptor, MET, MET Proto-Oncogene, Receptor Tyrosine Kinase
    2d
    Special Drug Use-results Surveillance of Tabrecta Tablets (clinicaltrials.gov)
    P=N/A, N=109, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET exon 14 mutation
    |
    Tabrecta (capmatinib)
    5d
    EGFR exon 20 insertion mutation and MET exon 14 skipping mutation in non-small cell lung cancer: a scoping review in the Chinese population. (PubMed, Transl Lung Cancer Res)
    Further large-scale studies are needed to establish links between these mutations and clinical features at baseline and following treatment. Furthermore, moving forward, the development of novel drugs will be essential to fulfill the clinical unmet needs.
    Review • Journal • EGFR exon 20
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    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR exon 20 insertion • MET exon 14 mutation • MET mutation
    5d
    Invasive mucinous adenocarcinoma harbored MET exon 14 skipping mutation: case report. (PubMed, Transl Lung Cancer Res)
    Molecular targeted drugs (tepotinib) showed similar efficacy for IMA harboring MET exon 14 skipping mutation to their use for NSCLC. This case suggests the benefit of aggressive multiplex genetic testing in patients with IMA and subsequent treatment with molecular targeted drugs.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • CEACAM5 (CEA Cell Adhesion Molecule 5)
    |
    MET exon 14 mutation
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    Tepmetko (tepotinib)
    6d
    Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials. (PubMed, Mil Med Res)
    A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBCs for the maximum efficiency of TK targeted therapeutics, either as standalone treatments or a combination. Moreover, our observation highlights that the outcomes of TK targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort, emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase)
    6d
    c-MET and the immunological landscape of cancer: novel therapeutic strategies for enhanced anti-tumor immunity. (PubMed, Front Immunol)
    This review also discusses the innovative cancer immunotherapies targeting c-MET, including chimeric antigen receptor (CAR) therapies, monoclonal antibodies, and antibody-drug conjugates, while encouraging the development of a comprehensive strategy that simultaneously tackles immune evasion and enhances anti-tumor efficacy further to improve the clinical prognoses for patients with c-MET-positive malignancies. Despite the challenges and variability in efficacy across different cancer subtypes, continued research into the molecular mechanisms and the development of innovative therapeutic strategies will be crucial.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET expression
    8d
    Precision medicine: an intrahepatic cholangiocarcinoma with a novel RBPMS-MET fusion sensitive to crizotinib. (PubMed, Oncologist)
    Our case report strengthens the evidence that crizotinib may be a viable treatment option for patients with ICC with a c-MET tyrosine kinase fusion, necessitating additional clinical investigation.
    Journal • PD(L)-1 Biomarker
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • RBPMS (RNA-binding protein with multiple splicing) • CA 19-9 (Cancer antigen 19-9)
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    MET fusion • RBPMS-MET fusion
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    Keytruda (pembrolizumab) • Xalkori (crizotinib) • gemcitabine • Lenvima (lenvatinib) • capecitabine
    9d
    Comprehensive review of signaling pathways and therapeutic targets in gastrointestinal cancers. (PubMed, Crit Rev Oncol Hematol)
    Targeted therapy, the milestone in the development of human medicine, originated in 2004 when the FDA approved the first targeted agent bevacizumab for colorectal cancer treatment...However, the efficacy of targeted therapy is extremely variable, especially with the emergence of new drugs and the innovative use of traditional targets for other tumors in recent years. Accordingly, this review provides an overview of the major signaling pathway mechanisms and recent advances in targeted therapy for gastrointestinal cancers, as well as future perspectives.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • CLDN18 (Claudin 18)
    |
    Avastin (bevacizumab)
    9d
    A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer. (PubMed, J Gastrointest Cancer)
    Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.
    P2 data • Journal • Metastases
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • RAS wild-type
    |
    Orpathys (savolitinib)
    9d
    Fluorescence based live cell imaging identifies exon 14 skipped hepatocyte growth factor receptor (MET) degraders. (PubMed, bioRxiv)
    We generated a library of sixty PROTACs of which 37 used the MET inhibitor capmatinib as the protein of interest targeting ligand...Curve fitting live cell imaging data affords determination of time required to degrade 50% of the target protein (DT50), which was used in determining structure activity relationships. A promising candidate, 48-284, identified from the screen, exhibited classic PROTAC characteristics, was > 15-fold more potent than SJF8240, had fewer off targets compared to SJF8240, and degraded MET in multiple cell lines.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET exon 14 mutation
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    Tabrecta (capmatinib)
    9d
    c-MET tyrosine kinase inhibitors reverse drug resistance mediated by the ATP-binding cassette transporter B1 (ABCB1) in cancer cells. (PubMed, 3 Biotech)
    Additionally, the combination of c-MET inhibitors with the chemotherapeutic agent doxorubicin synergistically enhanced cytotoxicity in MDR cells, as evidenced by combination index (CI) values of 0.54 ± 0.08, 0.69 ± 0.1, and 0.85 ± 0.07 for cabozantinib, crizotinib, and PHA665752, respectively...In silico analysis also suggested that the transmembrane domains (TMD) of ABCB1 transporters could be considered potential target for these agents. Our results suggest that c-MET inhibitors can serve as promising MDR reversal agents in ABCB1-medicated drug-resistant cancer cells.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • ABCB1 (ATP Binding Cassette Subfamily B Member 1)
    |
    Xalkori (crizotinib) • doxorubicin hydrochloride • Cabometyx (cabozantinib tablet) • PHA665752
    9d
    Hsa_circ_0009910 knockdown in HeLa cells increases miR‑198 expression levels and decreases c‑Met expression levels and cell viability. (PubMed, Oncol Lett)
    The hsa_circ_0009910/miRNA-198/c-Met interaction network affects the viability, but not apoptosis, of HeLa cells. Based on this mechanism, the present study suggests that hsa_circ_0009910 may be a promising biomarker for CC.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • MIR198 (MicroRNA 198)
    |
    MET expression
    11d
    Chimeric antigen receptor macrophages targeting c-MET(CAR-M-c-MET) inhibit pancreatic cancer progression and improve cytotoxic chemotherapeutic efficacy. (PubMed, Mol Cancer)
    This study provides compelling evidence for the safety and efficacy of CAR-M therapy in treating pancreatic cancer. The results demonstrate that CAR-M-c-MET significantly suppresses pancreatic cancer progression and enhances the effectiveness of cytotoxic chemotherapy. Remarkably, no discernible side effects occur. Further clinical trials are warranted in human pancreatic cancer patients.
    Journal • IO biomarker
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET expression
    12d
    Lung adenocarcinomas with mucinous histology: clinical, genomic, and immune microenvironment characterization and outcomes to immunotherapy-based treatments and KRASG12C inhibitors. (PubMed, Ann Oncol)
    LUADMuc represents a distinct LUAD subpopulation with unique clinicopathologic, genomic, immunophenotypic, and transcriptional features, achieving worse outcomes to standard immunotherapy-based treatments.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NKX2-1 (NK2 Homeobox 1) • GNAS (GNAS Complex Locus) • FOXP3 (Forkhead Box P3)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • ALK rearrangement • STK11 mutation • TMB-L • MET mutation
    13d
    Programmable Circular Multispecific Aptamer-Drug Engager to Broadly Boost Antitumor Immunity. (PubMed, J Am Chem Soc)
    The orchestrated innate and adaptive immunity effectively eliminated immunosuppressive MDSCs, Tregs, and M2-like macrophages in tumors and promoted the maturation of dendritic cells (DCs) in the draining lymph nodes, resulting in robust and durable systemic antitumor efficacy, with 7 out of 8 mice surviving over 60 days. Our programmable DNA-templated printing technology enables the rational design of multispecific therapeutics with modular composition and function but minimal production issues, providing a versatile tool for the development of multifunctional personalized medicine.
    Journal
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    MET (MET proto-oncogene, receptor tyrosine kinase) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • GZMB (Granzyme B)
    14d
    Deoxycholic acid aggravates necrotizing enterocolitis through downregulation of mesenchymal-epithelial transition factor expression. (PubMed, Braz J Med Biol Res)
    These findings indicated that MET mediated STAT3 involvement in intestinal epithelial cell proliferation and migration, demonstrating that the inhibitory effect of DCA on MET disrupted this process. These results elucidated the damaging effects and mechanisms of DCA accumulation in NEC, providing new insights into the use of DCA as a therapeutic target for NEC.
    Journal
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    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET expression
    14d
    Adenocarcinoma of the rete testis: clinicopathological study of 18 cases with emphasis on MET amplification and a review of the literature. (PubMed, Histopathology)
    Primary ACRT is a rare malignant tumour which poses a diagnostic challenge, and is associated with poor prognosis. Cases of ACRT with MET amplification might represent promising candidates for the treatment with MET inhibitors.
    Review • Journal
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    MET (MET proto-oncogene, receptor tyrosine kinase) • WT1 (WT1 Transcription Factor) • PAX8 (Paired box 8)
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    MET amplification
    14d
    Clinicopathological characteristics of Japanese patients with breast cancer and MET exon 14 skipping alterations. (PubMed, Histopathology)
    High c-MET expression and METex14s are common in apocrine carcinoma.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET exon 14 mutation • MET expression
    15d
    A universal immunohistochemistry analyzer for generalizing AI-driven assessment of immunohistochemistry across immunostains and cancer types. (PubMed, NPJ Precis Oncol)
    In a discovery application, the UIHC model assigned higher tumor proportion scores to MET amplification cases, but not MET exon 14 splicing or other non-small cell lung cancer cases. This UIHC model represents a novel role for DL that further advances quantitative analysis of IHC.
    Journal
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    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • MET exon 14 mutation
    15d
    Evolution of Rapid Clonal Dynamics and Non-Cross-Resistance in Response to Alternating Targeted Therapy and Chemotherapy in BRAF-V600E-Mutant Colon Cancer. (PubMed, JCO Precis Oncol)
    These findings suggest rational strategies for combining sequential chemotherapy and BRAF-/EGFR-directed therapy in BRAF-V600E-mutant colon cancer to prevent resistance and improve outcome. The data demonstrate rapid clonal dynamics in response to effective therapies in BRAF-V600E-mutant colon cancer that can be monitored by serial cfDNA analysis. Moreover, in mismatch repair-proficient BRAF-V600E-mutant colon cancers, combined EGFR and BRAF/MEK therapy is not cross-resistant with standard chemotherapy, suggesting new rational combination treatment strategies.
    Journal
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    BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
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    BRAF V600E • EGFR mutation • BRAF V600 • MET amplification
    19d
    LUNG-MAP Sub-Study: Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=124, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jun 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR T790M • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation
    |
    FoundationOne® CDx
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    Retevmo (selpercatinib)
    20d
    Geometry-N: Phase II of Neoadjuvant and Adjuvant Capmatinib in NSCLC (clinicaltrials.gov)
    P2, N=4, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; The study was terminated early due to recruitment challenges.
    Trial termination
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • MET exon 14 mutation • MET mutation
    |
    Tabrecta (capmatinib)
    21d
    Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test (clinicaltrials.gov)
    P1/2, N=10, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2028 --> Nov 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2028 --> Nov 2024; Sponsor Withdrew Support
    Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    HER-2 negative
    |
    CELsignia test
    |
    Nerlynx (neratinib) • Tabrecta (capmatinib)
    21d
    DB-1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov)
    P1/2, N=450, Recruiting, DualityBio Inc. | N=280 --> 450 | Trial completion date: Apr 2025 --> Sep 2026 | Trial primary completion date: Apr 2025 --> Sep 2026
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CD276 (CD276 Molecule)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK rearrangement • MET exon 14 mutation • ROS1 rearrangement • MET mutation • RET rearrangement • KRAS G12 • NTRK1 mutation
    |
    BNT324
    22d
    Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics. (PubMed, Mol Med)
    CAR macrophages targeting c-Met represent a promising therapeutic strategy for pancreatic cancer, offering targeted elimination of CSCs and disruption of tumor angiogenesis. This study highlights the potential of single-cell multi-omics in guiding the development of precision immunotherapies.
    Journal • IO biomarker
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    MET (MET proto-oncogene, receptor tyrosine kinase) • FGF2 (Fibroblast Growth Factor 2)
    |
    MET expression
    23d
    Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer. (PubMed, Onco Targets Ther)
    Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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    KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 mutation • RET fusion • ALK rearrangement • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • NRG1 fusion • KRAS G12 • NRG1 fusion • NTRK fusion
    23d
    Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer. (PubMed, Front Oncol)
    Some clinical trials based on this combined treatment approach have yielded promising preliminary results, offering more treatment options for NSCLC patients with TKI resistance. Additionally, early identification of resistance mechanisms through liquid biopsy, personalized targeted therapy against these mechanisms, and preemptive targeting of drug-tolerant persistent cells may provide NSCLC patients with more sustained and effective treatment.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase)
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    MET amplification • EGFR amplification
    27d
    Real-World Study on Implementation of Genomic Tests for Advanced Lung Adenocarcinoma in Brazil. (PubMed, JCO Glob Oncol)
    This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • PD-L1 overexpression • KRAS G12C • BRAF V600 • EGFR exon 20 insertion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • KRAS G12 • EGFR exon 20 mutation • ALK-ROS1 fusion • KRAS G12C + PD-L1 expression
    27d
    CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges. (PubMed, Front Immunol)
    We elucidate the therapeutic benefits of CAR T cells in HCC and identify the primary barriers to their broader application. Our analysis aims to provide a comprehensive overview of the current status and future prospects of CAR T-cell immunotherapy for HCC.
    Review • Journal • CAR T-Cell Therapy
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    MET (MET proto-oncogene, receptor tyrosine kinase) • GPC3 (Glypican 3) • NKG2D (killer cell lectin like receptor K1)
    28d
    Neratinib and Capmatinib Combination (Phase Ib/II) in Metastatic Breast Cancer and Inflammatory Breast Cancer Patients With Abnormal HER-family and c-Met Pathway Activity as Measured by the CELsignia Signaling Analysis Test (clinicaltrials.gov)
    P1/2, N=10, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=47 --> 10
    Enrollment closed • Enrollment change • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    HER-2 negative
    |
    CELsignia test
    |
    Nerlynx (neratinib) • Tabrecta (capmatinib)
    29d
    Effects of Neoadjuvant Therapy on Tumour Target Expression of Oesophageal Cancer Tissue for NIR Fluorescence Imaging. (PubMed, Mol Imaging Biol)
    EpCAM and EGFR appear to be the most suitable targets for tumour-specific NIR fluorescence imaging of oesophageal adenocarcinoma and squamous cell carcinoma, respectively. Unaffected expression of all suitable markers by neoadjuvant therapy implies that the diagnostic biopsy can be used to select a patient-specific target for response evaluation by molecular imaging.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • EPCAM (Epithelial cell adhesion molecule)
    |
    EPCAM expression
    30d
    Establishing a new human lung squamous cell carcinoma cell line, OMUL-1, expressing insulin-like growth factor 1 receptor and programmed cell death ligand 1. (PubMed, Thorac Cancer)
    We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.
    Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • FGFR4 (Fibroblast growth factor receptor 4) • IGF1R (Insulin-like growth factor 1 receptor) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • FLT4 (Fms-related tyrosine kinase 4) • NKX2-1 (NK2 Homeobox 1) • TP63 (Tumor protein 63)
    |
    PD-L1 expression • FGFR1 expression • IGF1R expression • FGFR2 expression • FGFR2b expression • FGFR3 expression • TTF1 negative
    |
    picropodophyllin (AXL1717)
    1m
    A Study to Assess Disease Activity of Intravenously (IV) Infused Telisotuzumab Vedotin in Adult Participants With Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P2, N=9, Terminated, AbbVie | Trial completion date: Mar 2026 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2025 --> Oct 2024; Strategic considerations
    Trial completion date • Trial termination • Trial primary completion date • Metastases
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification
    |
    telisotuzumab vedotin (ABBV-399)
    1m
    Saikosaponin-b2 Regulates the Proliferation and Apoptosis of Liver Cancer Cells by Targeting the MACC1/c-Met/Akt Signalling Pathway. (PubMed, Adv Pharmacol Pharm Sci)
    Additionally, the suppression of MACC1 activation by SS-b2 resulted in a reduction in the viability and proliferation of HepG2 liver cancer cells, and this reduction was comparable to that by doxorubicin (DOX)...Meanwhile, Annexin V-FITC/PI staining and western blot analysis of cleaved caspase 9 and cleaved caspase 3 demonstrated that SS-b2 induced apoptosis of HepG2 liver cancer cells. These findings provide experimental evidence suggesting that SS-b2 is a promising anticancer agent for liver cancer.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • CASP3 (Caspase 3) • CASP9 (Caspase 9) • MACC1 (MET Transcriptional Regulator MACC1) • ANXA5 (Annexin A5) • BAD (BCL2 Associated Agonist Of Cell Death)
    |
    MET expression
    |
    doxorubicin hydrochloride
    1m
    Impact of genomic alterations measured in circulating tumor DNA (ctDNA) on clinical response to telisotuzumab vedotin treatment in patients with non-small cell lung cancer (NSCLC) (AIOM 2024)
    METamp occurred more frequently in responders; but Teliso-V activity wasn’t restricted to these pts: most responders weren’t METamplified. Specific genomic alts beyond MET may influence clinical response. The current analysis demonstrated numeric differences between pts with identified drivers who did or didn’t respond to Teliso-V.
    Clinical • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS G12C • MET amplification • KRAS G12
    |
    Labcorp® Plasma Complete™
    |
    telisotuzumab vedotin (ABBV-399)
    1m
    Liquid Biopsy in Next Generation Sequencing (NGS) for tumor molecular profiling in advanced NSCLC in Umbria population: a realworld experience (AIOM 2024)
    Blood-based LB performed by NGS is a non-invasive viable alternative tool for molecular genotyping and identifiy tumor-derived somatic alterations to increase the number of pts elegible to target therapy and guide personalized medicine.
    Clinical • Real-world evidence • Liquid biopsy • Next-generation sequencing • Real-world • Metastases • Biopsy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • MET exon 14 mutation • KRAS G12 • KRAS exon 4 mutation
    |
    Oncomine™ Pan-Cancer Cell-Free Assay
    1m
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
    |
    FoundationOne® CDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    1m
    Genomic alterations in circulating tumor DNA (ctDNA) and response to ABBV-400 treatment in patients with advanced solid tumors (AIOM 2024)
    The ADC ABBV-400 comprises the c-Met–targeting antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload. ABBV-400 showed promising preliminary efficacy, with molecular and radiographic responses in pts with advanced solid tumors with heterogeneous genomic profiles, including pts with high TMB and KRAS mutations.
    Clinical • Tumor mutational burden • Circulating tumor DNA • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • MSI (Microsatellite instability) • LRP1B (LDL Receptor Related Protein 1B) • PTPRT (Protein tyrosine phosphatase receptor type T)
    |
    KRAS mutation • TMB-H • MET overexpression • PTPRT mutation
    |
    GuardantINFINITY™
    |
    telisotuzumab adizutecan (ABBV-400) • telisotuzumab (h224G11)
    1m
    Enhanced tumoricidal activity of PD-1 antibody-secreting c-Met CAR-T cells against pancreatic cancer cells (PubMed, Nan Fang Yi Ke Da Xue Xue Bao)
    PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.
    Journal • CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2)
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    PD-L1 expression • MET expression
    1m
    Targeted RNA Sequencing of Head and Neck Adenoid Cystic Carcinoma Reveals SEC16A::NOTCH1 Fusion and MET Exon 14 Skipping as Potentially Actionable Alterations. (PubMed, Head Neck Pathol)
    The study improved the understanding of AdCC providing the first documentation of tumor clinical behavior associated with MYB::MPDZ and FUS::MYB fusions and reporting potentially actionable SEC16A::NOTCH1 fusion and MET exon 14 skipping mutation. Further research is needed to explore the therapeutic utility of MET inhibition and the efficacy of γ-secretase inhibitors against rare NOTCH1 fusions in AdCC.
    Retrospective data • Journal • IO biomarker
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    MET (MET proto-oncogene, receptor tyrosine kinase) • NOTCH1 (Notch 1) • MYB (MYB Proto-Oncogene, Transcription Factor) • FUS (FUS RNA Binding Protein) • NFIB (Nuclear Factor I B) • MYBL1 (MYB Proto-Oncogene Like 1)
    |
    MET exon 14 mutation • MET mutation • MET D1010N • MYB-NFIB fusion
    1m
    Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies. (PubMed, Curr Res Pharmacol Drug Discov)
    This review explores the mechanisms by which c-Met contributes to chemoresistance in breast cancer and current challenges in targeting c-Met for breast cancer therapy. It discusses strategies to optimize treatment outcomes, ultimately improving patient prognosis and reducing mortality rates associated with this devastating disease.
    Review • Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET expression
    1m
    Discovery of N-substituted-2-oxoindolin benzoylhydrazines as c-MET/SMO modulators in EGFRi-resistant non-small cell lung cancer. (PubMed, RSC Med Chem)
    To address this unmet medical need, we explored the therapeutic potential of multitargeting agents that simultaneously inhibit two key signalling pathways, the mesenchymal-epithelial transition factor (c-MET) and the G protein-coupled receptor Smoothened (SMO), frequently dysregulated in NSCLC. By employing a combination of in silico drug repurposing and structure-based structure-activity relationship (SAR) studies, we identified and developed novel c-MET/SMO-targeting agents with antiproliferative activity against first- as well as third-generation EGFR-TKI-resistant NSCLC cells suggesting a synergistic effect arising from the simultaneous inhibition of c-MET and SMO.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    1m
    Evaluation of a Novel MET-Targeting Camelid-Derived Antibody in Head and Neck Cancer. (PubMed, Mol Pharm)
    Our preclinical data suggest that the camelid antibody 1E7-Fc could be a potential theranostic agent for HNSCC. Further investigations are warranted to confirm these findings in patients and to evaluate 1E7-Fc as an imaging agent and platform to deliver radionuclide or drug therapy to MET-driven cancers.
    Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET overexpression • MET expression