ArticleOncotarget2016
Long-term vemurafenib treatment drives inhibitor resistance through a spontaneous KRAS G12D mutation in a BRAF V600E papillary thyroid carcinoma model.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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Who cites it
50 citing papers in PubMed.
- Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Development and validation of theAnnals of medicine and surgery (2012) · 2026Article
- Targeting Sirtuins in Thyroid Cancer: Mechanisms, Drug Development, and Emerging Roles in Tumor Immunity and Ferroptosis.Cancers · 2026Review
- MAPK pathway inhibitors enhance radioiodine sensitivity in anaplastic thyroid carcinoma through promoting NIS expression and ARF4-mediated NIS membrane transport.Scientific reports · 2026Article
- Review
- Role of the ETV5/p38 Signaling Axis in Aggressive Thyroid Cancer Cells.Molecular cancer therapeutics · 2026Article
- Therapeutic Potential of Tyrosine Kinase Inhibitors in Advanced Thyroid Cancer.Current oncology reports · 2026Review
- Combination of astragalus polysaccharide with Diosbulbin B exerts an enhanced antitumor effect in BRAFCancer cell international · 2025Article
- Targeting endothelial growth factor receptor in thyroid cancer: current concepts and future directions.Medical oncology (Northwood, London, England) · 2025Review
- NOVEL INSIGHTS IN ADVANCED THYROID CARCINOMA: FROM MECHANISMS TO TREATMENTS: Molecular insights into the origin, biology, and treatment of anaplastic thyroid carcinoma.European thyroid journal · 2025Review
- Reimagining the Therapeutic Approach for Anaplastic Thyroid Cancer: The Roadmap to a Cure.Thyroid : official journal of the American Thyroid Association · 2025Review
- Exploring markers of immunoresponsiveness in papillary thyroid carcinoma and future treatment strategies.Journal for immunotherapy of cancer · 2024Article
- Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.International journal of molecular sciences · 2024Review
- Genomic alterations in thyroid cancer: biological and clinical insights.Nature reviews. Endocrinology · 2024Review
- Genetic alterations in thyroid cancer mediating both resistance to BRAF inhibition and anaplastic transformation.Oncotarget · 2024Article
- Emerging therapeutic options for follicular-derived thyroid cancer in the era of immunotherapy.Frontiers in immunology · 2024Review
- CombinationThyroid : official journal of the American Thyroid Association · 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
- Review
- Review
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Authors and funding
7 authors.
Funding
Abstract
The BRAF V600E mutation is commonly observed in papillary thyroid cancer (PTC) and predominantly activates the MAPK pathway. Presence of BRAF V600E predicts increasing risk of recurrence and higher mortality rate, and treatment options for such patients are limited. Vemurafenib, a BRAF V600E inhibitor, is initially effective, but cells inevitably develop alternative mechanisms of pathway activation. Mechanisms of primary resistance have been described in short-term cultures of PTC cells; however, mechanisms of acquired resistance have not. In the present study, we investigated possible adaptive mechanisms of BRAF V600E inhibitor resistance in KTC1 thyroid cancer cells following long-term vemurafenib exposure. We found that a subpopulation of KTC1 cells acquired resistance to vemurafenib following 5 months of treatment with the inhibitor. Resistance coincided with the spontaneous acquisition of a KRAS G12D activating mutation. Increases in activated AKT, ERK1/2, and EGFR were observed in these cells. In addition, the resistant cells were less sensitive to combinations of vemurafenib and MEK1 inhibitor or AKT inhibitor. These results support the KRAS G12D mutation as a genetic mechanism of spontaneously acquired secondary BRAF inhibitor resistance in BRAF V600E thyroid cancer cells.
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