ArticleBritish journal of cancer2010
Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy.
Article in British journal of cancer, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02583516 (A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma), which is not on this map. Cited by 153 papers, 2 of them syntheses 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.
A Randomized Phase II Study of Vemurafenib Plus Cobimetinib Continuous Versus Intermittent, in Previously Untreated BRAFV600- Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Who cites it
153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 312 citations in OpenAlex.
- Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.Journal for immunotherapy of cancer · 2021Pooled it
- The prognostic value of BRAF mutation in colorectal cancer and melanoma: a systematic review and meta-analysis.PloS one · 2012Pooled it
- Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma: A Phase 2 Clinical Trial.JAMA oncology · 2016Trial
- Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Trial
- Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations.The New England journal of medicine · 2012Trial
- ANXA1-Derived Peptide Increases Melanoma Cell Sensitivity to Vemurafenib by Downregulating EphA2.Journal of cellular and molecular medicine · 2026Article
- Article
- Drug Combinations Targeting FAK and MEK Overcomes Tumor Heterogeneity in Glioblastoma.Pharmaceutics · 2025Article
- Targeting BRAF pathway in low-grade serous ovarian cancer.Journal of gynecologic oncology · 2024Review
- Convenient synthesis and X-ray determination of 2-amino-6RSC advances · 2024Article
- Review
- Article
- Design and synthesis of new 1,2,4-oxadiazole/quinazoline-4-one hybrids with antiproliferative activity as multitargeted inhibitors.Frontiers in chemistry · 2024Article
- Defining melanoma combination therapies that provide senolytic sensitivity in human melanoma cells.Frontiers in cell and developmental biology · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2.International journal of molecular sciences · 2023Review
- Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Fibronectin Contributes to a BRAF Inhibitor-driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2.Molecular cancer research : MCR · 2023Article
- Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Pharmacological ascorbate induces sustained mitochondrial dysfunction.Free radical biology & medicine · 2023Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundResistance to BRAF inhibitors is an emerging problem in the melanoma field. Strategies to prevent and overcome resistance are urgently required.
methodsThe dynamics of cell signalling, BrdU incorporation and cell-cycle entry after BRAF inhibition was measured using flow cytometry and western blot. The ability of combined BRAF/MEK inhibition to prevent the emergence of resistance was demonstrated by apoptosis and colony formation assays and in 3D organotypic cell culture.
resultsBRAF inhibition led to a rapid recovery of phospho-ERK (pERK) signalling. Although most of the cells remained growth arrested in the presence of drug, a minor population of cells retained their proliferative potential and escaped from BRAF inhibitor therapy. A function for the rebound pERK signalling in therapy escape was demonstrated by the ability of combined BRAF/MEK inhibition to enhance the levels of apoptosis and abrogate the onset of resistance.
conclusionCombined BRAF/MEK inhibition may be one strategy to prevent the emergence of drug resistance in BRAF-V600E-mutated melanomas.
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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.