ReviewFrontiers in immunology2021
Selective Inhibitor of the c-Met Receptor Tyrosine Kinase in Advanced Hepatocellular Carcinoma: No Beneficial Effect With the Use of Tivantinib?
Review in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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, 25 citations in OpenAlex.
- Medicinal Chemistry of Small-Molecule c-Met Inhibitors: From Approved Therapies to Emerging Multitarget Anticancer Agents.International journal of molecular sciences · 2026Review
- Distinct cMET inhibitors uncover pharmacological heterogeneity in SHH medulloblastoma cell lines.Discover oncology · 2026Article
- Discovery of Novel c‑MET Inhibitors for Hepatocellular Carcinoma Using an Integrated Virtual Screening Approach.ACS medicinal chemistry letters · 2025Article
- Overexpression of c-Myc triggers p62 aggregation-mediated mitochondrial mitophagy in cabozantinib resistance of hepatocellular carcinoma.Molecular medicine (Cambridge, Mass.) · 2025Article
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Aberrant angiogenic signaling in HCC: therapeutic targeting and drug resistance.Frontiers in oncology · 2025Review
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- MET receptor serves as a promising target in melanoma brain metastases.Acta neuropathologica · 2024Article
- Recent advances in the treatment of non-small cell lung cancer with MET inhibitors.Frontiers in chemistry · 2024Review
- Targeting c-Met in breast cancer: From mechanisms of chemoresistance to novel therapeutic strategies.Current research in pharmacology and drug discovery · 2024Review
- New and Old Key Players in Liver Cancer.International journal of molecular sciences · 2023Review
- Translocations and Gene Fusions in Sinonasal Malignancies.Current oncology reports · 2023Review
- Receptor tyrosine kinase inhibitors in cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Advanced hepatocellular carcinoma (HCC) remains a formidable health challenge worldwide, with a 5-year survival rate of 2.4% in patients with distant metastases. The hepatocyte growth factor/cellular-mesenchymal-epithelial transition (HGF/c-Met) signaling pathway represents an encouraging therapeutic target for progressive HCC. Tivantinib, a non-adenosine triphosphate-competitive c-Met inhibitor, showed an attractive therapeutic effect on advanced HCC patients with high MET-expression in phase 2 study but failed to meet its primary endpoint of prolonging the overall survival (OS) in two phase 3 HCC clinical trials. Seven clinical trials have been registered in the "ClinicalTrials.gov" for investigating the safety and efficacy of tivantinib in treating advanced or unresectable HCC. Eight relevant studies have been published with results. The sample size ranged from 20 to 340 patients. The methods of tivantinib administration and dosage were orally 120/240/360 mg twice daily. MET overexpression was recorded at 34.6% to 100%. Two large sample phase 3 studies (the METIV-HCC study of Australia and European population and the JET-HCC study of the Japanese population) revealed that tivantinib failed to show survival benefits in advanced HCC. Common adverse events with tivantinib treatment include neutropenia, ascites, rash, and anemia, etc. Several factors may contribute to the inconsistency between the phase 2 and phase 3 studies of tivantinib, including the sample size, drug dosing, study design, and the rate of MET-High. In the future, high selective MET inhibitors combined with a biomarker-driven patient selection may provide a potentially viable therapeutic strategy for patients with advanced HCC.
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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.