ArticleMolecular therapy oncolytics2020
Dual Inhibition of MAPK and JAK2/STAT3 Pathways Is Critical for the Treatment of BRAF Mutant Melanoma.
Article in Molecular therapy oncolytics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Regulation and therapy, the role of JAK2/STAT3 signaling pathway in OA: a systematic review.Cell communication and signaling : CCS · 2023Pooled it
- Systematic Analysis of MRTFB Phosphoproteomic Datasets Reveals Co-Regulated Kinase Networks and Co-Occurring Phosphosites Associated with the Actin Cytoskeleton Pathway.Current issues in molecular biology · 2026Article
- IL-37 drives temozolomide resistance in glioblastoma via MAPK pathway activation.Oncology letters · 2026Article
- STAT3 signaling mediates EGFR-TKI resistance in non-small cell lung cancer by regulating stemness markers and telomerase, reversed by icaritin.British journal of cancer · 2026Article
- Dynamic Time-Resolved Remodeling of the Immune Microenvironment After Resistance to BRAF/MEK Inhibitors in Melanoma: Mechanisms, Biomarkers, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Resveratrol as a Dual MAPK/STAT3 Inhibitor in Glioblastoma: Mutation-Dependent Therapeutic Efficacy.Life (Basel, Switzerland) · 2026Article
- Ginsenoside Rg5 alleviates allergic rhinitis in rats by modulating nasal microbiota by inhibiting JAK2/STAT3/BCL-2 and MAPK signaling.Journal of ginseng research · 2026Article
- ERK1/2 hijack STAT3 via Thr714 phosphorylation to suppress gene expression.Cell communication and signaling : CCS · 2026Article
- IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review).International journal of oncology · 2026Review
- BRAF mutation and tumor immune microenvironment in new era.American journal of cancer research · 2026Review
- Bacterial colonized melanoma skin models allow to study host-microbe interactionsFrontiers in microbiology · 2026Article
- Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy.Cytokine & growth factor reviews · 2025Review
- Role of interleukin-6 in resistance to tumor therapy.Discover oncology · 2025Review
- Dihydrotanshinone I enhanced BRAF mutant melanoma treatment efficacy by inhibiting the STAT3/SOX2 signaling pathway.Frontiers in oncology · 2025Article
- Pyrimidine compounds BY4003 and BY4008 inhibit glioblastoma cells growth via modulating JAK3/STAT3 signaling pathway.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.Cancer cell international · 2024Article
- Molecular network mechanism of Shexiang Huayu Xingnao granules in treating intracerebral hemorrhage.Ibrain · 2024Article
- MEK Inhibition Synergizes with TYK2 Inhibitors in NF1-Associated Malignant Peripheral Nerve Sheath Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Ntrk1 promotes mesangial cell proliferation and inflammation in rat glomerulonephritis model by activating the STAT3 and p38/ERK MAPK signaling pathways.BMC nephrology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRAF and MEK inhibitors significantly prolong progression-free survival in patients with BRAF mutant melanoma. However, most patients quickly develop drug resistance. The mechanism of drug resistance is complicated and remains to be further explored. Here, we found that inhibition of the MAPK pathway activates the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, whereas JAK2 inhibitors that inhibit the JAK2/STAT3 pathway activate the MAPK pathway, suggesting a crosstalk between these two pathways in BRAF mutant melanoma cells. Reactivation of the MAPK pathway occurs in most drug-resistant patients with BRAF mutations. Therefore, dual inhibition of the MAPK and JAK2/STAT3 pathways is critical for the treatment of BRAF mutant melanoma. However, we found that the combination of BRAF, MEK inhibitors, and JAK2 or STAT3 inhibitors could not simultaneously inhibit the MAPK and JAK2/STAT3 pathways in BRAF mutant melanoma cells. Subsequently, we found that a combination of all three MAPK pathway inhibitors-BRAF, MEK, and ERK inhibitors-with JAK2 or STAT3 inhibitors can dually inhibit the MAPK and JAK2/STAT3 pathways, showing a significant inhibition of the growth of BRAF mutant melanoma cells compared with either treatment alone. Therefore, dual inhibition of MAPK and JAK2/STAT3 pathways may be a novel strategy for the treatment of BRAF mutant tumors.
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