ArticleJCI insight2018
Transcriptional targeting of oncogene addiction in medullary thyroid cancer.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Advances in Mechanism of Action and Efficacy of CBP/p300 Inhibitors in Different Subtypes of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- Targeted therapy in thyroid cancer: molecular alterations and clinical management.Frontiers in endocrinology · 2026Review
- Differential activity of specific inhibitors of transcription regulating cyclin-dependent kinases in thyroid cancer cells.Endocrine-related cancer · 2025Article
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Molecular docking and in vitro experiments verified that kaempferol induced apoptosis and inhibited human HepG2 cell proliferation by targeting BAX, CDK1, and JUN.Molecular and cellular biochemistry · 2023Article
- Molecular mechanisms of resistance to kinase inhibitors and redifferentiation in thyroid cancers.Endocrine-related cancer · 2022Review
- Article
- Functional impact of a germline RET mutation in alveolar rhabdomyosarcoma.Cold Spring Harbor molecular case studies · 2021Article
- circPVT1 regulates medullary thyroid cancer growth and metastasis by targeting miR-455-5p to activate CXCL12/CXCR4 signaling.Journal of experimental & clinical cancer research : CR · 2021Article
- ONC201 Shows Potent Anticancer Activity Against Medullary Thyroid Cancer via Transcriptional Inhibition ofMolecular cancer therapeutics · 2021Article
- New Horizons: Emerging Therapies and Targets in Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2021Review
- Targeting transcriptional regulators for treatment of anaplastic thyroid cancer.Journal of cancer metastasis and treatment · 2021Article
- Current and Future Role of Tyrosine Kinases Inhibition in Thyroid Cancer: From Biology to Therapy.International journal of molecular sciences · 2020Review
- Frequent genetic aberrations in the cell cycle related genes in mucosal melanoma indicate the potential for targeted therapy.Journal of translational medicine · 2019Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Metastatic medullary thyroid cancer (MTC) is incurable and FDA-approved kinase inhibitors that include oncogenic RET as a target do not result in complete responses. Association studies of human MTCs and murine models suggest that the CDK/RB pathway may be an alternative target. The objective of this study was to determine if CDKs represent therapeutic targets for MTC and to define mechanisms of activity. Using human MTC cells that are either sensitive or resistant to vandetanib, we demonstrate that palbociclib (CDK4/6 inhibitor) is not cytotoxic to MTC cells but that they are highly sensitive to dinaciclib (CDK1/2/5/9 inhibitor) accompanied by reduced CDK9 and RET protein and mRNA levels. CDK9 protein was highly expressed in 83 of 83 human MTCs and array-comparative genomic hybridization had copy number gain in 11 of 30 tumors. RNA sequencing demonstrated that RNA polymerase II-dependent transcription was markedly reduced by dinaciclib. The CDK7 inhibitor THZ1 also demonstrated high potency and reduced RET and CDK9 levels. ChIP-sequencing using H3K27Ac antibody identified a superenhancer in intron 1 of RET. Finally, combined inhibition of dinaciclib with a RET kinase inhibitor was synergistic. In summary, we have identified what we believe is a novel mechanism of RET transcription regulation that potentially can be exploited to improve RET therapeutic targeting.
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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.