ArticleBMC cancer2018
Pan-RAF and MEK vertical inhibition enhances therapeutic response in non-V600 BRAF mutant cells.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.Drugs in R&D · 2024Review
- Novel RAF-directed approaches to overcome current clinical limits and block the RAS/RAF node.Molecular oncology · 2024Review
- Development of Personalized Strategies for Precisely Battling Malignant Melanoma.International journal of molecular sciences · 2024Review
- Supramolecular Biomaterials for Cancer Immunotherapy.Research (Washington, D.C.) · 2023Review
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Experiments from unfinished Registered Reports in the Reproducibility Project: Cancer Biology.eLife · 2021Article
- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- Horizontal Combination of MEK and PI3K/mTOR Inhibition in BRAF Mutant Tumor Cells with or without Concomitant PI3K Pathway Mutations.International journal of molecular sciences · 2020Article
- Dual inhibition of CSF1R and MAPK pathways using supramolecular nanoparticles enhances macrophage immunotherapy.Biomaterials · 2020Article
- Article
- Synergistic inhibition of MEK and reciprocal feedback networks for targeted intervention in malignancy.Cancer biology & medicine · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundCurrently, there are no available targeted therapy options for non-V600 BRAF mutated tumors. The aim of this study was to investigate the effects of RAF and MEK concurrent inhibition on tumor growth, migration, signaling and apoptosis induction in preclinical models of non-V600 BRAF mutant tumor cell lines.
methodsSix BRAF mutated human tumor cell lines CRL5885 (G466 V), WM3629 (D594G), WM3670 (G469E), MDAMB231 (G464 V), CRL5922 (L597 V) and A375 (V600E as control) were investigated. Pan-RAF inhibitor (sorafenib or AZ628) and MEK inhibitor (selumetinib) or their combination were used in in vitro viability, video microscopy, immunoblot, cell cycle and TUNEL assays. The in vivo effects of the drugs were assessed in an orthotopic NSG mouse breast cancer model.
resultsAll cell lines showed a significant growth inhibition with synergism in the sorafenib/AZ628 and selumetinib combination. Combination treatment resulted in higher Erk1/2 inhibition and in increased induction of apoptosis when compared to single agent treatments. However, single selumetinib treatment could cause adverse therapeutic effects, like increased cell migration in certain cells, selumetinib and sorafenib combination treatment lowered migratory capacity in all the cell lines. Importantly, combination resulted in significantly increased tumor growth inhibition in orthotropic xenografts of MDAMB231 cells when compared to sorafenib - but not to selumetinib - treatment.
conclusionsOur data suggests that combined blocking of RAF and MEK may achieve increased therapeutic response in non-V600 BRAF mutant tumors.
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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.