ArticleMolecular cancer research : MCR2023
Activation of the JAK/STAT Pathway Leads to BRAF Inhibitor Resistance in BRAFV600E Positive Thyroid Carcinoma.
Article in Molecular cancer research : MCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 21 citations in OpenAlex.
- Review
- Review
- PTRF Confers Melanoma-Acquired Drug Resistance Through the Upregulation of EGFR.Cell proliferation · 2026Article
- Dendrobine inhibits anaplastic thyroid cancer progression by targeting the JAK-STAT3 pathway.Frontiers in oncology · 2026Article
- Tumor microenvironment remodeling across thyroid cancer differentiation states revealed by spatial transcriptomics.Cancer immunology, immunotherapy : CII · 2025Article
- Thyroid cancer: From molecular insights to therapy (Review).Oncology letters · 2025Review
- Post-translational modifications in anaplastic thyroid carcinoma: biological mechanisms and therapeutic potential.Cancer cell international · 2025Review
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 2025Review
- Article
- Small Molecule B-RAF Inhibitors as Anti-Cancer Therapeutics: Advances in Discovery, Development, and Mechanistic Insights.International journal of molecular sciences · 2025Review
- La-related protein 1 drives malignant progression and epithelial-mesenchymal transition in anaplastic thyroid carcinoma.American journal of cancer research · 2025Article
- Integrated single-cell and bulk transcriptomic analysis reveals shared pathogenesis and prognostic biomarkers in breast and thyroid cancers.Frontiers in immunology · 2025Article
- MicroRNA-mediated autophagy regulation in thyroid cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.Cell death & disease · 2024Article
- Dysregulated Signalling Pathways Driving Anticancer Drug Resistance.International journal of molecular sciences · 2023Review
- The Role of Inflammation-Associated Factors in Head and Neck Squamous Cell Carcinoma.Journal of inflammation research · 2023Review
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Authors and funding
21 authors at 1 institution in 1 country.
Funding
Abstract
A subset of thyroid cancers, recurrent differentiated thyroid cancers and anaplastic thyroid cancer (ATC), are difficult to treat by thyroidectomy and systemic therapy. A common mutation in thyroid cancer, BRAFV600E, has targetable treatment options; however, the results have been disappointing in thyroid cancers compared with BRAFV600E melanoma, as thyroid cancers quickly become resistant to BRAFV600E inhibitor (BRAFi). Here, we studied the molecular pathway that is induced in BRAFV600E thyroid cancer cells and patient-derived tumor samples in response to BRAFi, vemurafenib, using RNA-sequencing and molecular analysis. Both inducible response to BRAFi and acquired BRAFi resistance in BRAFV600E thyroid cancer cells showed significant activation of the JAK/STAT pathway. Functional analyses revealed that the combination of BRAFi and inhibitors of JAK/STAT pathway controlled BRAFV600E thyroid cancer cell growth. The Cancer Genome Atlas data analysis demonstrated that potent activation of the JAK/STAT signaling was associated with shorter recurrence rate in patients with differentiated thyroid cancer. Analysis of tumor RNA expression in patients with poorly differentiated thyroid cancer and ATC also support that enhanced activity of JAK/STAT signaling pathway is correlated with worse prognosis. Our study demonstrates that JAK/STAT pathway is activated as BRAFV600E thyroid cancer cells develop resistance to BRAFi and that this pathway is a potential target for anticancer activity and to overcome drug resistance that commonly develops to treatment with BRAFi in thyroid cancer. IMPLICATIONS: Dual inhibition of BRAF and JAK/STAT signaling pathway is a potential therapeutic treatment for anticancer activity and to overcome drug resistance to BRAFi in thyroid cancer.
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