Evidence map›Paper›PMID 41460609›Full record

ArticleCellular oncology (Dordrecht, Netherlands)2025

Organoid-based drug screening identifies homoharringtonine as a therapeutic agent for anaplastic thyroid cancer via TFEB-mediated lysosomal dysfunction.

Xinyue Zhang, Zhihui Li, Jiaye Liu, Rui Huang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Review
  2. 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.

Xinyue ZhangDepartment of Nuclear Medicine, West China Hospital, Sichuan University, No 37. Guoxue Alley, Chengdu, 610000, China.
Zhihui LiDivision of Thyroid Surgery, Department of General Surgery, Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, No 37. Guoxue Alley, Chengdu, 610000, China.
Jiaye LiuDivision of Thyroid Surgery, Department of General Surgery, Laboratory of Thyroid and Parathyroid Diseases, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, No 37. Guoxue Alley, Chengdu, 610000, China. liujiaye925@wchscu.cn.
Rui HuangDepartment of Nuclear Medicine, West China Hospital, Sichuan University, No 37. Guoxue Alley, Chengdu, 610000, China. huang_rui@scu.edu.cn.

Funding

1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University 23HXFH025National Nature Science Foundation of China NSFC82403761Science & Technology Department of Sichuan Province Science & Technology Department of Sichuan Province
6 · The paper itself

Abstract

purposeAnaplastic thyroid cancer (ATC) is a rare but aggressive malignancy with unmet clinical needs for novel therapeutic agents. Most prior studies have relied on limited ATC cell lines, which fail to recapitulate tumor heterogeneity. This study aimed to discover novel agent for ATC via patient-derived organoid (PDO)-based drug screening and investigate the underlying therapeutic mechanism.

methodsDrug screening was performed on ATC organoids using a drug library of stem cell differentiation compounds. RNA-sequencing identified pathway-level mechanisms, while structure-based molecular docking prioritized target proteins.

resultsUsing a library of stem cell differentiation compounds, we identified homoharringtonine (HHT) as a potent inhibitor for ATC growth in vitro and in vivo. Mechanistically, this effect was mediated by lysosomal dysfunction, which blocked autophagosome-lysosome fusion and triggered cytotoxicity. Furthermore, HHT exhibited high affinity for the PI3K p110 subunit, activating the PI3K-AKT-mTOR pathway to phosphorylate transcription factor EB, retaining it in the cytoplasm and thereby inhibiting lysosomal biogenesis.

conclusionOur study demonstrates the utility of cancer organoids in drug discovery and identifies HHT as a promising therapeuticagent for ATC.

Indexed as

HomoharringtonineLysosomesOrganoidsThyroid Carcinoma, AnaplasticThyroid NeoplasmsAnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCell Line, TumorCell ProliferationDrug Screening Assays, AntitumorHumansMicePhosphatidylinositol 3-KinasesSignal TransductionTOR Serine-Threonine KinasesBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsHomoharringtoninePhosphatidylinositol 3-KinasesTFEB protein, humanTOR Serine-Threonine KinasesAnaplastic thyroid cancerDrug repurposingDrug screeningLysosomal autophagyPatient-derived organoid

Identifiers

PMID41460609
PMCPMC12748095

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.