ArticleCancer gene therapy2021
An organoid-based drug screening identified a menin-MLL inhibitor for endometrial cancer through regulating the HIF pathway.
Article in Cancer gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Bioengineering trends in female reproduction: a systematic review.Human reproduction update · 2022Pooled it
- Organoids: Current Applications and Future Directions.MedComm · 2026Review
- Engineering the Human Endometrial-Embryo Interface: Breakthroughs in 3D Uterine Models.Biomolecules · 2026Review
- Exosome-derived Menin from cancer-associated fibroblasts promotes gastric cancer progression by activating the HSPA6/JNK/JunD pathway and inducing EMT.Journal of translational medicine · 2025Article
- Engineering human endometrial model systems in reproductive health and disease.npj biomedical innovations · 2025Review
- Predicted peptide scaffolds for drug screening in endometrial cancer organoids.Scientific reports · 2025Article
- Menin regulates YBX1 nucleus translocation to boost the HKDC1 transcription and affects pancreatic cancer glycolysis.iScience · 2025Article
- Imaging 3D cell cultures with optical microscopy.Nature methods · 2025Review
- Menin: from molecular insights to clinical impact.Epigenomics · 2025Review
- Epigenetic mechanisms underlying endometrial cancer outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival.Carcinogenesis · 2025Article
- Organoid development and applications in gynecological cancers: the new stage of tumor treatment.Journal of nanobiotechnology · 2025Review
- Development and Application of Tumor Organoids: An Emerging Platform for Gynecological Cancers.International journal of women's health · 2025Review
- Preclinical research models for endometrial cancer: development and selection of animal models.Frontiers in oncology · 2025Review
- Organoid modeling meets cancers of female reproductive tract.Cell death discovery · 2024Review
- Menin in Cancer.Genes · 2024Review
- Bioengineering approaches for the endometrial research and application.Materials today. Bio · 2024Review
- Research progress on the application of organoids in gynecological tumors.Frontiers in pharmacology · 2024Review
- Exploring the black box of human reproduction: endometrial organoids and assembloids - generation, implantation modeling, and future clinical perspectives.Frontiers in cell and developmental biology · 2024Review
- A New Type of Endometrial Cancer Models in Mice Revealing the Functional Roles of Genetic Drivers and Exploring their Susceptibilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Menin-MLL1 Interaction Small Molecule Inhibitors: A Potential Therapeutic Strategy for Leukemia and Cancers.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor organoids recapitulate pathological properties and would serve as an excellent ex vivo model for drug discovery. Here, we performed an unbiased drug screening on drivers-defined tumor organoids from mouse endometrial cancer, the most prevalent gynecological malignancy in human, with a small molecule library targeting epigenetic factors. Among them, menin-MLL inhibitors MI-136 and MI-463 scored. The therapeutic capacity of MI-136 was further validated in tumor organoids in vitro and an orthotopic model in vivo. CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136. Transcriptome analysis showed that the hypoxia-inducible factor (HIF) pathway was the most significantly downregulated pathway by MI-136 treatment. Consistently, Men1, Kmt2a, and Ash2l knockout also repressed the expressions of the HIF target genes. Loss of Hif1a or Hif1b partially phenocopied the inhibition of the menin-MLL complex by MI-136 or mutations in term of tumor organoid growth. Further, we found that MEN1 was upregulated in human endometrial cancers, which were tightly correlated with the expression levels of HIF1A, and associated with poor prognosis. Importantly, MI-136 also significantly inhibited the growth of endometrial cancer organoids derived from patients. Thus, our study identified MI-136 as a potential inhibitor for endometrial cancer through regulating the HIF pathway, a novel molecular mechanism distinguished from those in AML and prostate cancer.
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Registered trials
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