ArticleScientific reports2019
Modeling the Effect of the Metastatic Microenvironment on Phenotypes Conferred by Estrogen Receptor Mutations Using a Human Liver Microphysiological System.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A quantitative meta-analysis comparing cell models in perfused organ on a chip with static cell cultures.Scientific reports · 2023Pooled it
- Scaling human liver microphysiological systems: implementing a higher-throughput liver acinus microphysiological system platform.Experimental biology and medicine (Maywood, N.J.) · 2026Article
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- Integrated Patient Digital and Biomimetic Twins for Precision Medicine: A Perspective.Seminars in liver disease · 2025Review
- Comparison of wild-type and high-risk PNPLA3 variants in a human biomimetic liver microphysiology system for metabolic dysfunction-associated steatotic liver disease precision therapy.Frontiers in cell and developmental biology · 2024Article
- Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling.In vitro models · 2023Review
- Organ-On-A-Chip Database Revealed-Achieving the Human Avatar in Silicon.Bioengineering (Basel, Switzerland) · 2022Review
- A Quantitative Systems Pharmacology Platform Reveals NAFLD Pathophysiological States and Targeting Strategies.Metabolites · 2022Article
- Targeting Metabolic Adaptations in the Breast Cancer-Liver Metastatic Niche Using Dietary Approaches to Improve Endocrine Therapy Efficacy.Molecular cancer research : MCR · 2022Article
- Quantifying the progression of non-alcoholic fatty liver disease in human biomimetic liver microphysiology systems with fluorescent protein biosensors.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Atorvastatin facilitates chemotherapy effects in metastatic triple-negative breast cancer.British journal of cancer · 2021Article
- Integrative microphysiological tissue systems of cancer metastasis to the liver.Seminars in cancer biology · 2021Review
- Human biomimetic liver microphysiology systems in drug development and precision medicine.Nature reviews. Gastroenterology & hepatology · 2021Review
- Applications of the microphysiology systems database for experimental ADME-Tox and disease models.Lab on a chip · 2020Article
- Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology.Handbook of experimental pharmacology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Reciprocal coevolution of tumors and their microenvironments underlies disease progression, yet intrinsic limitations of patient-derived xenografts and simpler cell-based models present challenges towards a deeper understanding of these intercellular communication networks. To help overcome these barriers and complement existing models, we have developed a human microphysiological system (MPS) model of the human liver acinus, a common metastatic site, and have applied this system to estrogen receptor (ER)+ breast cancer. In addition to their hallmark constitutive (but ER-dependent) growth phenotype, different ESR1 missense mutations, prominently observed during estrogen deprivation therapy, confer distinct estrogen-enhanced growth and drug resistant phenotypes not evident under cell autonomous conditions. Under low molecular oxygen within the physiological range (~5-20%) of the normal liver acinus, the estrogen-enhanced growth phenotypes are lost, a dependency not observed in monoculture. In contrast, the constitutive growth phenotypes are invariant within this range of molecular oxygen suggesting that ESR1 mutations confer a growth advantage not only during estrogen deprivation but also at lower oxygen levels. We discuss the prospects and limitations of implementing human MPS, especially in conjunction with in situ single cell hyperplexed computational pathology platforms, to identify biomarkers mechanistically linked to disease progression that inform optimal therapeutic strategies for patients.
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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.