ArticleCancer research2015
Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in Metastatic Uveal Melanoma.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 64 citations in OpenAlex.
- Transcriptome Alterations in Liver Metastases of Colorectal Cancer After Acquired Resistance to Cetuximab.Cancer genomics & proteomicsTrial
- GNAQ Induces Melanomagenesis in Mitfa-Independent Melanocyte Progenitors in a Zebrafish Model of Uveal Melanoma.Cancer research · 2026Article
- Structure, mechanism and clinical relevance of NRG1 fusions in cancer.Journal of biomedical science · 2026Review
- Zhoushi Qiling decoction inhibits neuregulin 1 secreted from cancer-associated fibroblasts to ameliorate enzalutamide resistance in prostate cancer.Journal of traditional and complementary medicine · 2026Article
- Systematic profiling of cancer-fibroblast interactions reveals drug combinations in ovarian cancer.Molecular oncology · 2025Article
- Current Therapies and Potential Strategies for Uveal Melanoma.Drugs and drug candidates · 2025Article
- Genetics and current research models of Mendelian tumor predisposition syndromes with ocular involvement.Progress in retinal and eye research · 2025Review
- Molecular characterization of Chinese patients with small bowel adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Review
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- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Role of Fibroblast Growth Factors in the Crosstalk of Hepatic Stellate Cells and Uveal Melanoma Cells in the Liver Metastatic Niche.International journal of molecular sciences · 2022Article
- Treatment of Metastatic Melanoma with a Combination of Immunotherapies and Molecularly Targeted Therapies.Cancers · 2022Review
- Potential Biomarkers of Skin Melanoma Resistance to Targeted Therapy-Present State and Perspectives.Cancers · 2022Review
- Met-HER3 crosstalk supports proliferation via MPZL3 in MET-amplified cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
- Adjuvant crizotinib in high-risk uveal melanoma following definitive therapy.Frontiers in oncology · 2022Article
- Targeting Oncogenic GαCancers · 2021Review
- Article
- Review
- Rational design of a potent macrocyclic peptide inhibitor targeting the PD-1/PD-L1 protein-protein interaction.RSC advances · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Uveal melanoma patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually targeting ERBB3 and cMET, the receptors for NRG1 and HGF, respectively, overcome resistance to trametinib provided by these growth factors and by conditioned medium from fibroblasts that produce NRG1 and HGF. Inhibition of AKT also effectively reverses the protective effect of NRG1 and HGF in trametinib-treated cells. Uveal melanoma xenografts growing in the liver in vivo and a subset of liver metastases of uveal melanoma patients express activated forms of ERBB2 (the coreceptor for ERBB3) and cMET. Together, these results provide preclinical evidence for the use of MEK inhibitors in combination with clinical-grade anti-ERBB3 or anti-cMET monoclonal antibodies in metastatic uveal melanoma.
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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.