ArticleOncotarget2019
Failures in preclinical and clinical trials of c-Met inhibitors: evaluation of pathway activity as a promising selection criterion.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- MET pathway inhibition increases chemo-immunotherapy efficacy in small cell lung cancer.Cell reports. Medicine · 2025Article
- Unlocking the therapeutic potential of antibody-drug conjugates in targeting molecular biomarkers in non-small cell lung cancer.Journal of the Egyptian National Cancer Institute · 2025Review
- Deciphering molecular pathways driving cancer invasion and metastasis: advances and therapeutic prospects.Frontiers in oncology · 2025Review
- Advancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin.Cells · 2024Article
- Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies.Current research in pharmacology and drug discovery · 2024Review
- Lupeol synergizes with 5-fluorouracil to combat c-MET/EphA2 mediated chemoresistance in triple negative breast cancer.iScience · 2023Article
- Review
- Automatic Multi-functional Integration Program (AMFIP) towards all-optical mechano-electrophysiology interrogation.PloS one · 2022Article
- Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer.International journal of molecular sciences · 2021Review
- The role of MET in chemotherapy resistance.Oncogene · 2021Review
- Synthesis and biological evaluation of novel (Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Therapeutic Efficacy of ABN401, a Highly Potent and Selective MET Inhibitor, Based on Diagnostic Biomarker Test inCancers · 2020Article
- Synergistic enhancement of efficacy of platinum drugs with verteporfin in ovarian cancer cells.BMC cancer · 2020Article
- TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors.Molecular oncology · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
C-Met is a frequently overexpressed or amplified receptor tyrosine kinase involved in metastatic-related functions, including migration, invasion, cell survival, and angiogenesis. Because of its role in cancer progression and metastasis, many inhibitors have been developed to target this pathway. Unfortunately, most c-Met inhibitor clinical trials have failed to show significant improvement in survival of cancer patients. In these trials tumor type, protein overexpression, or gene amplification are the primary selection criteria for patient inclusion. Our data show that none of these criteria are associated with c-Met pathway activation. Hence, it is conceivable that the majority of c-Met inhibitor clinical trial failures are the consequence of a lack of appropriate patient selection. Further complicating matters, c-Met inhibitors are routinely tested in preclinical studies in the presence of high levels of exogenous Hepatocyte Growth Factor (HGF), its activating ligand. In our studies, several tumor cell lines showed sensitivity to a c-Met inhibitor at high HGF concentrations (50 ng/mL). However, when the tumor lines were tested at HGF levels typically detected in human serum (0.4 to 0.8 ng/mL), inhibitor activity was lost. Thus testing c-Met inhibitors at non-physiological concentrations of HGF may lead to incorrect predictions of drug efficacy
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.