ArticleJournal of translational medicine2011
Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations.
Article in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Effect of metformin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from real-world studies.Prostate cancer and prostatic diseases · 2025Pooled it
- RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors.The New England journal of medicine · 2012Trial
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Combined cold atmospheric plasma and vemurafenib suppress MITF-P21 signaling and MMP-driven metastasis in cutaneous melanoma.Iranian journal of basic medical sciences · 2026Article
- Treatment resistance to melanoma therapeutics on a single cell level.Scientific reports · 2024Article
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Metabolic Reprogramming in Thyroid Cancer.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes.Drug design, development and therapy · 2023Review
- BRAF activation by metabolic stress promotes glycolysis sensitizing NRASNature communications · 2022Article
- Pharmacological inhibition of Ref-1 enhances the therapeutic sensitivity of papillary thyroid carcinoma to vemurafenib.Cell death & disease · 2022Article
- Metabolic Plasticity in Melanoma Progression and Response to Oncogene Targeted Therapies.Cancers · 2021Review
- Synergistic effect of metformin and vemurufenib (PLX4032) as a molecular targeted therapy in anaplastic thyroid cancer: an in vitro study.Molecular biology reports · 2021Article
- A common goal to CARE: Cancer Advocates, Researchers, and Clinicians Explore current treatments and clinical trials for breast cancer brain metastases.NPJ breast cancer · 2021Review
- Potential effect of EGCG on the anti-tumor efficacy of metformin in melanoma cells.Journal of Zhejiang University. Science. B · 2021Article
- Antitumor Effect of Metformin in Combination with Binimetinib on Melanoma Cells.Development & reproduction · 2021Article
- Screening of metabolic modulators identifies new strategies to target metabolic reprogramming in melanoma.Scientific reports · 2021Article
- A Novel Mitochondrial Inhibitor Blocks MAPK Pathway and Overcomes MAPK Inhibitor Resistance in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- Synergistic Enhancement of Paclitaxel-induced Inhibition of Cell Growth by Metformin in Melanoma Cells.Development & reproduction · 2019Article
- Article
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 3 institutions in 2 countries.
Funding
Abstract
backgroundA molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines. MATERIALS AND
methodsThe combination of the BRAF inhibitor vemurafenib (formerly PLX4032) and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot.
resultsSingle agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants, including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways.
conclusionsThe combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.
Indexed as
Identifiers
What OpenQuestion holds
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.