ArticleCancer biology & therapy2014
Targeting c-Met in melanoma: mechanism of resistance and efficacy of novel combinatorial inhibitor therapy.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 43 citations in OpenAlex.
- Review
- Clinical Molecular Pathology and Treatment Developments in Advanced Uveal Melanoma: State of the Art.Oncology research · 2026Review
- Ultraviolet Radiation Biological and Medical Implications.Current issues in molecular biology · 2024Review
- Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma.Cancer research communications · 2023Article
- Expression and Prognostic Evaluation of the Receptor Tyrosine Kinase MET in Canine Malignant Melanoma.Veterinary sciences · 2023Article
- MET Signaling Pathways, Resistance Mechanisms, and Opportunities for Target Therapies.International journal of molecular sciences · 2022Review
- Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.Cancers · 2022Review
- Dysregulation of Wnt/β-catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application.Cancer science · 2021Review
- RTK Inhibitors in Melanoma: From Bench to Bedside.Cancers · 2021Review
- Review
- Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.Cell death & disease · 2020Article
- Targeting the HGF/MET Axis in Cancer Therapy: Challenges in Resistance and Opportunities for Improvement.Frontiers in cell and developmental biology · 2020Review
- Towards dual inhibitors of the MET kinase and WNT signaling pathway; design, synthesis and biological evaluation.RSC advances · 2019Article
- Adult and iPS-derived non-parenchymal cells regulate liver organoid development through differential modulation of Wnt and TGF-β.Stem cell research & therapy · 2019Article
- HGF/c-MET Signaling in Melanocytes and Melanoma.International journal of molecular sciences · 2018Review
- Article
- Gefitinib or lapatinib with foretinib synergistically induce a cytotoxic effect in melanoma cell lines.Oncotarget · 2018Article
- Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma.Molecular cancer · 2018Review
- Role Played by Signalling Pathways in Overcoming BRAF Inhibitor Resistance in Melanoma.International journal of molecular sciences · 2017Review
- StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.Cancer medicine · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous tyrosine kinase inhibitors (TKIs) targeting c-Met are currently in clinical trials for several cancers. Their efficacy is limited due to the development of resistance. The present study aims to elucidate this mechanism of c-Met TKI resistance by investigating key mTOR and Wnt signaling proteins in melanoma cell lines resistant to SU11274, a c-Met TKI. Xenografts from RU melanoma cells treated with c-Met TKIs SU11274 and JNJ38877605 showed a 7- and 6-fold reduction in tumor size, respectively. Resistant cells displayed upregulation of phosphorylated c-Met, mTOR, p70S6Kinase, 4E-BP1, ERK, LRP6, and active β-catenin. In addition, GATA-6, a Wnt signaling regulator, was upregulated, and Axin, a negative regulator of the Wnt pathway, was downregulated in resistant cells. Modulation of these mTOR and Wnt pathway proteins was also prevented by combination treatment with SU11274, everolimus, an mTOR inhibitor, and XAV939, a Wnt inhibitor. Treatment with everolimus, resulted in 56% growth inhibition, and a triple combination of SU11274, everolimus and XAV939, resulted in 95% growth inhibition in RU cells. The V600E BRAF mutation was found to be positive only in MU cells. Combination treatment with a c-Met TKI and a BRAF inhibitor displayed a synergistic effect in reducing MU cell viability. These studies indicate activation of mTOR and Wnt signaling pathways in c-Met TKI resistant melanoma cells and suggest that concurrent targeting of c-Met, mTOR, and Wnt pathways and BRAF may improve efficacy over traditional TKI monotherapy in melanoma patients.
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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.