ArticleProceedings of the National Academy of Sciences of the United States of America2014
p53 constrains progression to anaplastic thyroid carcinoma in a Braf-mutant mouse model of papillary thyroid cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.
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Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- Genomic Heterogeneity and Exceptional Response to Dual Pathway Inhibition in Anaplastic Thyroid Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Pooled it
- Dabrafenib Versus Dabrafenib + Trametinib inThyroid : official journal of the American Thyroid Association · 2022Trial
- Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study.Annals of oncology : official journal of the European Society for Medical Oncology · 2022Trial
- 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
- Single-Cell Transcriptome of Anaplastic Thyroid Cancer Reveals Immunosuppressive Tumor Microenvironment Remodeling.Cancer medicine · 2026Article
- Microenvironmental Control of Thyroid Cancer Plasticity and Radioiodine Resistance.International journal of molecular sciences · 2026Review
- Convergent Mechanistic Pathways Driving the Anaplastic Phenotype in Thyroid Cancer.International journal of molecular sciences · 2026Review
- Role of the ETV5/p38 Signaling Axis in Aggressive Thyroid Cancer Cells.Molecular cancer therapeutics · 2026Article
- Article
- Deciphering functional intra-tumoral heterogeneity in BRAFOncogene · 2026Article
- Mechanism of cancer-associated fibroblast-driven thyroid cancer dedifferentiation via the ZFP57-PKM2 axis-mediated lactate secretion and therapeutic intervention with resveratrol.Journal of experimental & clinical cancer research : CR · 2026Article
- Cancer Stemness and Dedifferentiation in Anaplastic Thyroid Carcinoma: Insights into a Multigenic, Microenvironmental Network and the Role of CD44.Biomedicines · 2026Review
- Retroelements in thyroid cancer: epigenetic plasticity, dedifferentiation, and therapeutic opportunities.Reviews in endocrine & metabolic disorders · 2026Review
- Dedifferentiation and Redifferentiation of Follicular-Cell-Derived Thyroid Carcinoma: Mechanisms and Therapeutic Implications.Biomedicines · 2025Review
- Sex differences in thyroid aging and their implications in thyroid disorders: insights from gene regulatory networks.bioRxiv : the preprint server for biology · 2025Article
- Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells.European thyroid journal · 2025Review
- Anaplastic thyroid cancer: Genetic roles, targeted therapy, and immunotherapy.Genes & diseases · 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
- Integrative proteogenomic characterization reveals therapeutic targets in poorly differentiated and anaplastic thyroid cancers.Nature communications · 2025Article
- Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of papillary thyroid carcinoma via the BRAF-ERK1/2-P53 signaling pathway.Journal of endocrinological investigation · 2025Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Anaplastic thyroid carcinoma (ATC) has among the worst prognoses of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. v-raf murine sarcoma viral oncogene homolog B (BRAF) and tumor protein p53 (TP53) mutations cooccur in a high proportion of ATCs, particularly those associated with a precursor papillary thyroid carcinoma (PTC). To develop an adult-onset model of BRAF-mutant ATC, we generated a thyroid-specific CreER transgenic mouse. We used a Cre-regulated Braf(V600E) mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from PTC to ATC. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis, and rapid lethality. We used small-animal ultrasound imaging to monitor autochthonous tumors and showed that treatment with the selective BRAF inhibitor PLX4720 improved survival but did not lead to tumor regression or suppress signaling through the MAPK pathway. The combination of PLX4720 and the mapk/Erk kinase (MEK) inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small-molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma.
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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.