ArticleOncotarget2018
Type II RAF inhibitor causes superior ERK pathway suppression compared to type I RAF inhibitor in cells expressing different BRAF mutant types recurrently found in lung cancer.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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
26 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Antitumor effects of CEP32496 on urothelial carcinoma with BRAF mutation (V595E) in dogs.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2026Article
- Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors.Molecular medicine (Cambridge, Mass.) · 2025Article
- AZ-628 sensitizes donafenib in hepatocellular carcinoma by targeting tyrosine kinase pathway and ferroptosis.CytoJournal · 2025Article
- Advances in Understanding Drug Resistance Mechanisms and Innovative Clinical Treatments for Melanoma.Current treatment options in oncology · 2024Review
- Revisiting the Role of B-RAF Kinase as a Therapeutic Target in Melanoma.Current medicinal chemistry · 2024Article
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- Unique Spectrum of Activating BRAF Alterations in Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Enzalutamide-induced signatures revealed by epigenetic plasticity using single-cell multi-omics sequencing in prostate cancer.Molecular therapy. Nucleic acids · 2023Article
- Mechanistic model of MAPK signaling reveals how allostery and rewiring contribute to drug resistance.Molecular systems biology · 2023Article
- Review
- BRAF-mediated brain tumors in adults and children: A review and the Australian and New Zealand experience.Frontiers in oncology · 2023Review
- Review
- BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies.Current treatment options in oncology · 2022Review
- Review
- Article
- Discovery of Raf Family Is a Milestone in Deciphering the Ras-Mediated Intracellular Signaling Pathway.International journal of molecular sciences · 2022Review
- A structural perspective on targeting the RTK/Ras/MAP kinase pathway in cancer.Protein science : a publication of the Protein Society · 2021Review
- ECMarker: interpretable machine learning model identifies gene expression biomarkers predicting clinical outcomes and reveals molecular mechanisms of human disease in early stages.Bioinformatics (Oxford, England) · 2021Article
- Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a Pyridopyridazinone pan-RAF Kinase Inhibitor.ACS medicinal chemistry letters · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A large fraction of somatic driver BRAF mutations in lung cancer are non-V600 and impaired-kinase. Non-V600 BRAF mutations predict sensitivity to combination of a type I RAF inhibitor, Dabrafenib, and a MEK inhibitor, Trametinib. Singly, Dabrafenib only weakly suppresses mutant BRAF-induced ERK signaling and can induce ERK paradoxical activation in CRAF-overexpressing cells. The present study compared the effects of Dabrafenib and a type II RAF inhibitor, AZ628, on ERK activity in HEK293T cells expressing several tumor-derived BRAF mutants, and in a non-V600 and impaired-kinase BRAF-mutant lung cancer cell line (H1666). Unlike Dabrafenib, AZ628 did not induce paradoxical ERK activation in CRAF-overexpressing cells and BRAF-mutant cells overexpressing CRAF were more responsive to AZ628 compared to Dabrafenib in terms of ERK inhibition. AZ628 inhibited ERK more effectively than Dabrafenib in both H1666 cells and HEK293T cells co-expressing several different BRAF-mutants with CRAF. Similarly, AZ628 plus Trametinib had better MEK-inhibitory and pro-apoptotic effects in H1666 cells than Dabrafenib plus Trametinib. Moreover, prolonged treatment of H1666 cells with AZ628 plus Trametinib produced greater inhibition of cell growth than Dabrafenib plus Trametinib. These results indicate that AZ628 has greater potential than Dabrafenib, both as a single agent and combined with Trametinib, for the treatment of non-V600 BRAF mutant lung cancer.
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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.