ArticleOncotarget2016
The mTOR inhibitor Everolimus synergizes with the PI3K inhibitor GDC0941 to enhance anti-tumor efficacy in uveal melanoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Mutational Characteristics of Primary Mucosal Melanoma: A Systematic Review.Molecular diagnosis & therapy · 2022Pooled it
- Redox Homeostasis, Metabolic Pathways and Plasticity in Uveal Melanoma Compared to Other Cancers.Cancers · 2026Review
- Complex Inhibitory Activity of Pentacyclic Triterpenoids against Cutaneous Melanoma In Vitro and In Vivo: A Literature Review and Reconstruction of Their Melanoma-Related Protein Interactome.ACS pharmacology & translational science · 2024Review
- TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target.Oncogene · 2024Article
- PKC-independent PI3K signalling diminishes PKC inhibitor sensitivity in uveal melanoma.Oncogenesis · 2024Article
- Biological characteristics and clinical management of uveal and conjunctival melanoma.Oncology research · 2024Review
- Predicting anticancer synergistic drug combinations based on multi-task learning.BMC bioinformatics · 2023Article
- Patient Derived Xenografts (PDX) Models as an Avatar to Assess Personalized Therapy Options in Uveal Melanoma: A Feasibility Study.Current oncology (Toronto, Ont.) · 2023Article
- Article
- FAK Inhibitor-Based Combinations with MEK or PKC Inhibitors Trigger Synergistic Antitumor Effects in Uveal Melanoma.Cancers · 2023Article
- Novel Treatments of Uveal Melanoma Identified with a Synthetic Lethal CRISPR/Cas9 Screen.Cancers · 2022Article
- An Orthotopic Model of Uveal Melanoma in Zebrafish Embryo: A Novel Platform for Drug Evaluation.Biomedicines · 2021Article
- Targeting Oncogenic GαCancers · 2021Review
- Review
- Dual Inhibition of Histone Deacetylases and the Mechanistic Target of Rapamycin Promotes Apoptosis in Cell Line Models of Uveal Melanoma.Investigative ophthalmology & visual science · 2021Article
- The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice.International journal of molecular sciences · 2021Article
- Mouse models of uveal melanoma: Strengths, weaknesses, and future directions.Pigment cell & melanoma research · 2020Review
- Uveal melanoma: progress in molecular biology and therapeutics.Therapeutic advances in medical oncology · 2020Review
- Emerging Therapeutic Opportunities Based on Current Knowledge of Uveal Melanoma Biology.Cancers · 2019Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Uveal melanoma (UM) is the most frequent malignant ocular tumor in adults. While the primary tumor is efficiently treated by surgery and/or radiotherapy, about one third of UM patients develop metastases, for which no effective treatment is currently available. The PKC, MAPK and PI3K/AKT/mTOR signaling cascades have been shown to be associated with tumor growth. However, none of the compounds against those pathways results in tumor regression when used as single agents. To identify more effective therapeutic strategies for UM patients, we performed a combination screen using seven targeted agents inhibiting PKC, MEK, AKT, PI3K and mTOR in a panel of ten UM cell lines, representative of the UM disease. We identified a strong synergy between the mTOR inhibitor Everolimus and the PI3K inhibitor GDC0941. This combination resulted in an increase in apoptosis in several UM cell lines compared to monotherapies and enhanced the anti-tumor effect of each single agent in two patient-derived xenografts. Furthermore, we showed that the synergism between the two drugs was associated with the relief by GDC0491 of a reactivation of AKT induced by Everolimus. Altogether, our results highlight a novel and effective combination strategy, which could be beneficial for UM 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.