ArticlePigment cell & melanoma research2016
Synergistic targeted inhibition of MEK and dual PI3K/mTOR diminishes viability and inhibits tumor growth of canine melanoma underscoring its utility as a preclinical model for human mucosal melanoma.
Article in Pigment cell & melanoma research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- The Comparative Oncology of Canine Malignant Melanoma in Targeted Therapy: A Systematic Review ofInternational journal of molecular sciences · 2024Pooled it
- Phytochemical profile and proteomic landscape associated with antineoplastic activity ofVeterinary and animal science · 2026Article
- Preclinical and Virtual Models of Mucosal Melanoma: Bridging Translational Gaps in a Rare and Lethal Cancer.Pigment cell & melanoma research · 2026Review
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- The Roles of PTEN in Melanoma Suppression.Pigment cell & melanoma research · 2025Review
- Capacity for Compensatory Cyclin D2 Response Confers Trametinib Resistance in Canine Mucosal Melanoma.Cancers · 2025Article
- Article
- Capacity for compensatory cyclin D2 response confers trametinib resistance in canine mucosal melanoma.bioRxiv : the preprint server for biology · 2025Article
- The MEK inhibitor trametinib is effective in inhibiting the growth of canine oral squamous cell carcinoma.Scientific reports · 2025Article
- Exploring the Epidemiology of Melanocytic Tumors in Canine and Feline Populations: A Comprehensive Analysis of Diagnostic Records from a Single Pathology Institution in Italy.Veterinary sciences · 2024Article
- Opportunities for targeted therapies: trametinib as a therapeutic approach to canine oral squamous cell carcinomas.Research square · 2024Article
- Article
- Protein phosphatase 6 regulates trametinib sensitivity, a mitogen-activated protein kinase kinase (MEK) inhibitor, by regulating MEK1/2-ERK1/2 signaling in canine melanoma cells.The Journal of veterinary medical science · 2023Article
- Comparative oncology: overcoming human cancer through companion animal studies.Experimental & molecular medicine · 2023Review
- mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma.Frontiers in oncology · 2023Article
- Effects of Para-Toluenesulfonamide on Canine Melanoma Xenotransplants in a BALB/c Nude Mouse Model.Animals : an open access journal from MDPI · 2022Article
- Antitumor activity of the dual PI3K/mTOR inhibitor gedatolisib and the involvement of ABCB1 in gedatolisib resistance in canine tumor cells.Oncology reports · 2022Article
- Molecular Genetic Investigation of Digital Melanoma in Dogs.Veterinary sciences · 2022Article
- Pharmacokinetics and tolerability of the dual TORC1/2 inhibitor sapanisertib in combination with the MEK inhibitor trametinib in dogs.Frontiers in veterinary science · 2022Article
- Inhibition of Axl Promotes the Therapeutic Effect of Targeted Inhibition of the PI3K/Akt Pathway in NRAS Mutant Melanoma Cells.Journal of oncology · 2022Article
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 6 institutions in 1 country.
Funding
Abstract
Human mucosal melanoma (MM), an uncommon, aggressive and diverse subtype, shares characteristics with spontaneous MM in dogs. Although BRAF and N-RAS mutations are uncommon in MM in both species, the majority of human and canine MM evaluated exhibited RAS/ERK and/or PI3K/mTOR signaling pathway activation. Canine MM cell lines, with varying ERK and AKT/mTOR activation levels reflective of naturally occurring differences in dogs, were sensitive to the MEK inhibitor GSK1120212 and dual PI3K/mTOR inhibitor NVP-BEZ235. The two-drug combination synergistically decreased cell survival in association with caspase 3/7 activation, as well as altered expression of cell cycle regulatory proteins and Bcl-2 family proteins. In combination, the two drugs targeted their respective signaling pathways, potentiating reduction of pathway mediators p-ERK, p-AKT, p-S6, and 4E-BP1 in vitro, and in association with significantly inhibited solid tumor growth in MM xenografts in mice. These findings provide evidence of synergistic therapeutic efficacy when simultaneously targeting multiple mediators in melanoma with Ras/ERK and PI3K/mTOR pathway activation.
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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.