Evidence map›Paper›PMID 31272080›Full record

ArticleEndocrine-related cancer2019

Potentiated anti-tumor effects of BETi by MEKi in anaplastic thyroid cancer.

Xuguang Zhu, Sunmi Park, Woo Kyung Lee, Sheue-Yann Cheng

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrine-related cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 22 citations in OpenAlex.

  1. Modulation ofInternational journal of molecular sciences · 2026
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  17. New Horizons: Emerging Therapies and Targets in Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2021
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Xuguang ZhuLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Sunmi ParkLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Woo Kyung LeeLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Sheue-Yann ChengLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Center for Cancer Research · USNational Cancer Institute · USNational Institutes of Health · US

Funding

Thyroid Hormone Receptors in Health and DiseaseZ01BC008752 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CHENG, SHEUE-YANN · 1996 to 2008
$2.5M
Intramural NIH HHS Z01 BC008752
6 · The paper itself

Abstract

Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options. We explored novel treatment modalities by targeting epigenetic modifications using inhibitors of BET (e.g. BRD4) activity. We evaluated the efficacy in the treatment of ATC of a novel BET inhibitor, PLX51107 (PLX), currently in clinical trials for other solid tumors and hematologic malignancies, alone or combined with a MEK inhibitor, PD0325901(PD). To elucidate the effects of these inhibitors on growth of ATC, we treated ATC cells derived from patient tumors (THJ-11T and THJ-16T cells) and mouse xenograft tumors with inhibitors. We found PLX and PD inhibitors singly inhibited proliferation of both human ATC cells lines, but together exhibited stronger inhibition of proliferation. In mouse xenografts, the combination treatment almost totally blocked growth in xenograft tumors derived from both ATC cells. PD effectively attenuated MEK-ERK signaling, which was further enhanced by PLX in the combined treatment in cultured cells and tumors. Importantly, the combination of PLX and PD acted synergistically to suppress MYC transcription to increase p27 in decreasing tumor cell proliferation. PLX and PD cooperated to upregulate pro-apoptotic proteins to promote apoptosis. These two inhibitors converged to reduce the binding of BRD4 to the MYC promoter to suppress the MYC expression. These findings indicate that combined treatment of BET and MEK-ERK inhibitors was more effective to treat ATC than single targeted treatment. Synergistic suppression of MYC transcription via collaborative actions on chromatin modifications suggested that targeting epigenetic modifications could provide novel treatment opportunities for ATC.

Indexed as

AnimalsAntineoplastic Combined Chemotherapy ProtocolsApoptosisBenzamidesBromodomain Containing ProteinsCell Cycle ProteinsCell ProliferationDiphenylamineDrug SynergismFemaleHumansMAP Kinase Kinase 1MiceMice, NudeOxazolesPyridinesBenzamidesBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsDiphenylamineMAP Kinase Kinase 1mirdametinibOxazolesPLX51107PyridinesPyrrolesTranscription Factorsanaplastic thyroid cancerbromodomain and extraterminal protein inhibitorPD0325901PLX51107tumorigenesis

Identifiers

PMID31272080
PMCPMC6938575
OpenAlexW2955452453

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.