MET expression

Our study establishes that the MUC5AC/cMET/CD44v6 axis is critical for BCBrM, and blocking this axis will be a novel therapeutic approach for BCBrM.

The abundant expression of cellular MET (c-MET) in cancer cells has provided new opportunities for immuno-oncology approaches in a broader patient population, and the integration of MET-targeted personalized medicine with immunotherapy has not been fully exploited yet. Here, we highlight essential facets of MET as a therapeutic target in NSCLC and provide an outlook for future approaches.

We divided the results by subsite for markers: lymph node analysis (microRNAs, myosin-5a (MYO5A), ring finger protein 145 (RNF145), F-box only protein 32 (FBXO32), CTONG2002744, cytokeratin 14 (CK14), eukaryotic initiation factor 4E (eIF4E), desmoglein-3 (DSG3), microsatellite D9S171, squamous cell carcinoma antigen, cytokeratin, tumor budding score, human papillomavirus-DNA (HPV-DNA), tumor infiltrating lymphocytes, sentinel lymph node analysis techniques, single fiber reflectance spectroscopy, radiological techniques), tumor tissue analysis (activin A, carcinoma-associated fibroblasts, cyclins, β-catenin, histopathology, genetic amplifications, DNA methylation, ecotropic viral integration site 1, CC-chemokine receptor 7, melanoma associated-A antigens, vascular endothelial growth factor-C (VEGF-C), panitumumab, epidermal growth factor receptor (EGFR), cornulin, total protein analysis, CD133, NANOG homeobox, neurogenic locus notch homolog protein 1 (NOTCH1), metastasis-associated protein 1, 14-3-3-zeta, E-cadherin, focal adhesion kinase, p-epithelial-mesenchymal transition (EMT), small proline rich protein 1B (SPRR1B), transcription factor NKX3-1, DNA copy number aberrations, microfibril-associated protein 5 (MFAP5), troponin C1, slow skeletal and cardiac type (TNNC1), matrix Gla protein (MGP), fibroblast growth factor binding protein 1 (FBFBP1), F-box protein 32 (FBXO32), fatty acid binding protein 5, B cell-specific Moloney murine leukemia virus integration site 1, podoplanin, p53, Bcl-2, epidermal growth factor receptor (EGFR), Ki67, cyclin D1, cox-2, semaphorin-3F, neuropilin-2, histologic features, cellular dissociation grade, prospero homeobox protein 1, radiologic features, Ki-67, poly (ADP-ribose) polymerase (PARP), Bcl-2 associated agonist of cell death (BAD), caspase-9, vascular endothelial growth factor A (VEGF-A), HPV, p16, methylation status of long interspersed element 1 (LINE-1) and Alu elements, mesenchymal-epithelial transition (MET), gene expression analyses, molecular subtypes) and blood markers (standard blood analysis indexes and ratios, circulating tumor cells, HPV-DNA, CD-31, bone marrow analysis). Several promising markers were identified, including miR-205, desmoglein 3 (DSG3), pan-cytokeratin (CK) AE1/AE3, HPV-16, activin-A, cyclin D1, E-cadherin, and neural progenitor lineage (NPL) that demonstrated effectiveness across multiple studies. Future research should focus on exploring combination scoring systems to improve diagnostic precision and optimize treatment selection in HNSCC patients.

P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Feb 2025 --> Jun 2026

Canine HCC may involve different angiogenesis mechanisms. CT findings can be used to assess the gene expression status in canine HCC and may add new value to CT imaging.

Moreover, MET expression was decreased in HSF4-knockdown cells but elevated in sunitinib-resistant RCC cells...Furthermore, HSF4 knockdown combined with an ICI showed synergistic suppression of tumor growth in vivo. Overall, our strategy involving HSF4 knockdown may enhance the efficacy of existing therapies, such as cabozantinib and ICIs.

In the TCGA database, the MET expressions were upregulated in oral cancer tissues compared to normal tissues, and were correlated with poor cell differentiated and poorer prognoses in smoker groups. In conclusion, these novel findings underscore the role of MET genetic variants in oral cancer susceptibility, particularly in smokers, and highlight the potential of these variants for prognosis and disease prediction.

The SMYD2-EZH2 expressions and c-MET activation were notably suppressed by OC treatments in vitro and in collected animal primary tumors. OC and olive phenolics are potential nutraceutical interventions useful for CRC control and the prevention of its relapse.

The probe effectively imaged c-Met-positive tumors and demonstrated a favorable metabolism profile and targeting performance in non-small cell lung cancer (NSCLC) or colorectal cancer tumor models. Consequently, this probe shows promise as an imaging agent capable of providing valuable diagnostic insights into tumors with aberrant c-Met expression.

P4, N=20, Beijing Hospital; Beijing Hospital

Teliso-V plus osimertinib had promising activity and a manageable safety profile in patients with c-Met protein-overexpressing, EGFR-mutated non-squamous NSCLC after progression on osimertinib. This combination has the potential to address an unmet medical need in this patient population.

P2, N=152, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

Tumor xenograft experiments demonstrated that coptisine effectively inhibited tumor growth by reducing the levels of pyroptosis-associated proteins. In conclusion, these findings indicate that inhibition of the HGF/c-Met signaling pathway suppresses pyroptosis to enhance the antitumor effect of coptisine in ESCC and support the potential use of coptisine for EC treatment.

P=N/A, N=32, Not yet recruiting, Tarsus University

Findings from our study add to the growing evidence on the potential crosstalk between MET and estrogen receptors in breast cancer. The expression of the MET/ESR genes could be a novel prognosticator and calls for future studies to evaluate the impact of combinational treatment approaches with MET inhibitors and endocrine drugs in breast cancer.

Moreover, this amphiphilic DNA nanotweezer shows enhanced accumulation at the tumor site and the inhibition of tumor growth. Taking advantage of the stimuli-responsive membrane anchoring capability, this reconfigurable DNA nanotweezer could be further explored as a smart multifunctional platform for cancer therapy.

There is a possible correlation between c-MET and HER2 gene overexpression and poor clinical outcomes in patients with BC.

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.

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.

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.

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.

High c-MET expression and METex14s are common in apocrine carcinoma.

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.

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.

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.

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.

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.

EMI-137 accumulates in dysplastic lesions within BE and in c-MET positive EAC. EMI-137 imaging has potential as a screening and surveillance tool for patients with BE and as a means to detecting dysplasia and EAC.

P=N/A, N=180, Active, not recruiting, University of Malaga

Overall, the research highlights the critical role of targeting c-Met to address osimertinib resistance in NSCLC. By demonstrating the efficacy of xanthohumol in overcoming resistance and enhancing therapeutic outcomes, this study provides valuable insights and potential new strategies for improving the clinical management of NSCLC.

Overall, our data indicate that c-MET directly regulates NB growth and 3D spheroid growth, and c-MET inhibition by tivantinib may be an effective therapeutic approach for high-risk NB. Further developing c-MET targeted therapeutic approaches and combining them with current therapies may pave the way for effectively translating novel therapies for NB and other c-MET-driven cancers.

P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=460 --> 701

A 43-year-old, female diagnosed with T4N3M1c NSCLC harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variant 1 (EML4-ALK v.1) and TP53 co-mutation, displayed only mixed response after three months and highly symptomatic progression after 6 months of first-line brigatinib treatment. The latter may represent a mechanism of intrinsic ALK-TKI resistance and its recognition by FISH, in NGS-negative cases, may be considered before initiating first-line treatment. This recognition is clinically important as combined therapy with ALK-TKI and MET-inhibitor should be the preferred first-line treatment.

The expression of the PD-L1 and MET genes is remarkably associated with worse tumor clinicopathologic features and poor prognosis in patients with breast cancer. Further investigations using combination drug regimens targeting PD-L1 and MET are important, particularly in breast tumors expressing high levels of both proteins.

P1, N=177, Completed, Haihe Biopharma Co., Ltd. | Unknown status --> Completed | N=75 --> 177

Finally, by performing a comparative transcriptomic analysis, we identify target genes that could play a relevant role in these cellular processes. Thus, our results demonstrate for the first time in prostate cancer models a functional interaction between ETS transcription factors (ETV1 and ERG) and MET signalling that confers more aggressive properties and highlight a molecular signature characteristic of this combined action.

CSL1-II in a weakly acidic environment had a stronger inhibitory effect on the HGF/c-Met pathway and exerted a strong controlling effect on the spreading and migration of cancer cells. Our strategy provides a simple and versatile method to develop pH-responsive DNA aptamers and represents the first example of a cancer-selective c-Met antagonist that inhibits cell migration.

EPHA2 expression is also related to aging and smoking habits. The expression levels of the TAM and EPHA2 genes seem to play an important role in breast cancer, being also influenced by the patient's lifestyle.

P=N/A, N=630, Recruiting, University Hospital, Clermont-Ferrand | Not yet recruiting --> Recruiting

Importantly, rAd.mDCN.mCD40L and rAd.mCD40L prevented tumor liver metastasis much more effectively than rAd.Null and rAd.mDCN. Therefore, rAd.mDCN.mCD40L and rAd.mCD40L are promising approaches for CRC therapy.

P1/2, N=231, Active, not recruiting, Regeneron Pharmaceuticals | N=82 --> 231 | Trial completion date: Oct 2024 --> Jan 2032 | Trial primary completion date: Oct 2024 --> Jan 2032

MET is an important contributor to acid-driven colorectal cancer metastasis and participates in immune escape of colorectal cancer. It is of great significance for the prognosis and immunotherapy of colorectal cancer and some other cancers.