ArticleOncogene2014
Combined PKC and MEK inhibition for treating metastatic uveal melanoma.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Identification of novel chemotherapeutic strategies for metastatic uveal melanoma.Scientific reports · 2017Pooled it
- Independent and synergistic roles of MEK-ERK1/2 and PKC pathways in regulating functional changes in vascular tissue following flow cessation.Journal of molecular and cellular cardiology plus · 2025Article
- Darovasertib, a novel treatment for metastatic uveal melanoma.Frontiers in pharmacology · 2023Review
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma.Frontiers of medicine · 2022Article
- Review
- Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor.Cancers · 2022Article
- Article
- Clinicopathological and prognostic significance and molecular mechanisms governing uveal melanoma.Therapeutic advances in medical oncology · 2020Review
- Article
- An insight into the molecular genetics of a uveal melanoma patient cohort.Journal of cancer research and clinical oncology · 2018Article
- Targeted silencing of the ADP-ribosyltransferase 3 gene inhibits the migration ability of melanoma cells.Oncology letters · 2018Article
- Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles.Oncotarget · 2016Article
- Opposing roles of conventional and novel PKC isoforms in Hippo-YAP pathway regulation.Cell research · 2015Article
- Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in Metastatic Uveal Melanoma.Cancer research · 2015Article
- Radiation therapy, cytogenetic prognostication, novel systemic chemotherapy, and patient perspective in an adult with choroidal melanoma.CA: a cancer journal for cliniciansArticle
Corrections and comments
- Comment on
Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Uveal melanoma (UM) is the most common primary intraocular malignancy and the second most common form of melanoma. UM has a strong tendency for metastatic disease, and no effective treatments have yet been identified. Activating oncogenic mutations are commonly found in GNAQ and GNA11 in UM, and inhibiting key downstream effectors of the GNAQ/11 signaling pathway represents a rational therapeutic approach for treating metastatic UM. Chen et al., doi:10.1038/onc.2013.418, now confirm activation of the MAPK and PKC pathways as a result of GNAQ and GNA11 activating mutations in melanocytes, and they demonstrate that MAPK activation occurs downstream of PKC activation. PKC inhibitors disrupt MAPK signaling and block proliferation of GNAQ/11 mutant UM cell lines and slow the in vivo growth of xenografted UM tumors without inducing their shrinkage. However, a combination of PKC and MEK inhibition led to sustained MAPK pathway inhibition and tumor regression in vivo. Hence, the authors concluded that MEK and PKC inhibition is synergistic, with superior efficacy to treatment of GNAQ/GNA11 mutant UMs with either drug alone.
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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.