ArticleThe Journal of clinical investigation2016
Sustained ERK inhibition maximizes responses of BrafV600E thyroid cancers to radioiodine.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 2 of them syntheses that pooled it.
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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
74 citing papers in PubMed, 2 syntheses or guidelines pooled it, 136 citations in OpenAlex.
- BRAF/MEK inhibitors for redifferentiation in patients with radioiodine refractory thyroid cancer: A systematic review and Meta-Analysis.Endocrine · 2026Pooled it
- 2025 American Thyroid Association Management Guidelines for Adult Patients with Differentiated Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2025Guideline
- Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Enhancing Radioiodine Incorporation inThyroid : official journal of the American Thyroid Association · 2022Trial
- ERK Signaling in Thyroid Cancer: Lineage Suppression, Epigenetic Reprogramming, and Theranostic Reversal.Cancers · 2026Review
- Microenvironmental Control of Thyroid Cancer Plasticity and Radioiodine Resistance.International journal of molecular sciences · 2026Review
- MAPK pathway inhibitors enhance radioiodine sensitivity in anaplastic thyroid carcinoma through promoting NIS expression and ARF4-mediated NIS membrane transport.Scientific reports · 2026Article
- No reinduction of clinically relevant radioiodine uptake after lenvatinib treatment in radioidine-refractory differentiated thyroid cancer.European journal of nuclear medicine and molecular imaging · 2026Article
- Treatment with Kinase Inhibitors Plus Myo-Inositol as Re-Differentiating Agents in Iodine-Refractory Thyroid Cancers.Life (Basel, Switzerland) · 2026Article
- How to manage radioiodine-refractory thyroid cancer in the era of precision medicine.Drugs in context · 2026Review
- Article
- Epigenetic control in thyroid cancer: mechanisms and clinical perspective.Cell death discovery · 2025Review
- Feasibility of Short-Term Redifferentiation in Patients with Radioactive Iodine-Refractory Metastatic Thyroid Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Redifferentiation therapy in unresectable or metastatic radioactive iodine refractory thyroid cancer: an International Thyroid Oncology Group statement.The lancet. Diabetes & endocrinology · 2025Review
- Systemic Therapeutic Options in Radioiodine-Refractory Differentiated Thyroid Cancer: Current Indications and Optimal Timing.Cancers · 2025Review
- Enhancing radioactive iodine (RAI) incorporation in RAI-refractory differentiated thyroid cancer: current insights.European thyroid journal · 2025Review
- HMGA2 Overexpression in Papillary Thyroid Cancer Promotes Thyroid Cell Dedifferentiation and Invasion, and These Effects Are Counteracted by Suramin.International journal of molecular sciences · 2025Article
- Application and recent advances in conventional biomarkers for the prognosis of papillary thyroid carcinoma.Frontiers in oncology · 2025Review
- Pathogenesis and Management Strategies in Radioiodine-Refractory Differentiated Thyroid Cancer: From Molecular Mechanisms Toward Therapeutic Approaches: A Comprehensive Review.Journal of clinical medicine · 2024Review
- Redifferentiation Therapies in Thyroid Oncology: Molecular and Clinical Aspects.Journal of clinical medicine · 2024Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer. Although the MEK inhibitor selumetinib transiently inhibited ERK signaling, which subsequently rebounded, the MEK inhibitor CKI suppressed ERK signaling in a sustained manner by preventing RAF reactivation. A small increase in ERK inhibition markedly increased the expression of thyroid differentiation genes, increased iodide accumulation in cancer cells, and thereby improved responses to RAI therapy. Only a short exposure to the drug was necessary to obtain a maximal response to RAI. These data suggest that potent inhibition of ERK signaling is required to adequately induce iodide uptake and indicate that this is a promising strategy for the treatment of BRAF-mutant thyroid 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.