ArticleCellular and molecular gastroenterology and hepatology2019
Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells.
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Article in Cellular and molecular gastroenterology and hepatology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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92citing papers in PubMed, 1 pooled it
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- A systematic review on the culture methods and applications of 3D tumoroids for cancer research and personalized medicine.Cellular oncology (Dordrecht, Netherlands) · 2025Pooled it
- Establishment and functional characterization of an EGFR-amplified tumoroid from squamous cell carcinoma of unknown primary.Human cell · 2026Article
- Patient-derived lung organoids from bronchoalveolar lavage capture epithelial heterogeneity and disease biology in bronchopulmonary dysplasia.Redox biology · 2026Article
- The advancements in organoids: Potential and challenges in researching the esophagus and esophageal squamous cell carcinoma.Genes & diseases · 2026Review
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- Advances in oral disease models: a mini-review of developments from 2015 to 2025.Frontiers in dental medicine · 2026Review
- Targeting c-Myc-p300-CARM1 complex induces ferroptosis and reduces CD8International journal of biological sciences · 2026Article
- Organoid-based two-step drug screening for rapid identification of chemotherapy-resistant oesophageal squamous cell carcinoma and alternative therapies.Clinical and translational medicine · 2025Article
- Chelerythrine inhibits esophageal squamous cell carcinoma progression via PINK1-Parkin-mediated mitophagy.Journal of translational medicine · 2025Article
- Head and neck tumor organoid grown under simplified media conditions model tumor biology and chemoradiation responses.Scientific reports · 2025Article
- Combination of tumor organoids with advanced technologies: A powerful platform for tumor evolution and treatment response (Review).Molecular medicine reports · 2025Review
- Patient-derived esophageal adenocarcinoma organ chip: a physiologically relevant platform for functional precision oncology.Journal of translational medicine · 2025Article
- An organoid library of human esophageal squamous cell carcinomas (ESCCs) uncovers the chemotherapy-resistant ESCC features.Communications biology · 2025Article
- CD133-Guided RNA Nanoparticle Delivery of FTO siRNA Impairs Leukemia Resistance to Tyrosine Kinase Inhibitor Therapy.RNA nanomed · 2025Article
- Establishment and characterization of novel patient-derived esophageal tumoroids with long-term cultivability.Human cell · 2025Article
- Squamous cell cancers of the aero-upper digestive tract: A unified perspective on biology, genetics, and therapy.Cancer cell · 2025Review
- Modeling methods of different tumor organoids and their application in tumor drug resistance research.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Biomedical applications of organoids derived from the digestive system.Frontiers in cell and developmental biology · 2025Review
- Novel research model for in vitro immunotherapy: co-culturing tumor organoids with peripheral blood mononuclear cells.Cancer cell international · 2024Review
- Advancing precision medicine in esophageal squamous cell carcinoma using patient-derived organoids.Journal of translational medicine · 2024Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 9 institutions in 2 countries.
Takashi KijimaDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Hiroshi NakagawaDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania. Electronic address: nakagawh@pennmedicine.upenn.edu.
Masataka ShimonosonoDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; Division of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania.
Prasanna M ChandramouleeswaranDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania.
Takeo HaraDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Varun SahuDepartment of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Yuta KasagiDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Osamu KikuchiDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Koji TanakaDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania; Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Veronique GirouxDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania.
Amanda B MuirDivision of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Kelly A WhelanDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania; Fels Institute for Cancer Research & Molecular Biology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
Shinya OhashiDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Seiji NaganumaDepartment of Pathology, Kochi University School of Medicine, Nankoku, Japan.
Andres J Klein-SzantoHistopathology Facility and Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Yoshiaki ShindenDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Ken SasakiDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Itaru OmotoDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Yoshiaki KitaDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Manabu MutoDepartment of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Adam J BassDana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, Massachusetts.
J Alan DiehlDepartment of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.
Gregory G GinsbergDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania.
Yuichiro DokiDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Masaki MoriDepartment of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Yasuto UchikadoDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Takaaki ArigamiDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Narayan G AvadhaniDepartment of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Devraj BasuDepartment of Otorhinolaryngology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
Anil K RustgiDivision of Gastroenterology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania. Electronic address: anil2@pennmedicine.upenn.edu.
Shoji NatsugoeDepartment of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. Electronic address: natsugoe@m2.kufm.kagoshima-u.ac.jp.
University of Pennsylvania · USKagoshima University · JPOsaka University · JPKyoto University · JPChildren's Hospital of Philadelphia · USFox Chase Cancer Center · USHarvard University · USKōchi University · JPMedical University of South Carolina · US
Funding
Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3MTRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Ken Hashigiwa Cadwell · 1997 to 2026
$32.5MTransformed Esophageal Epithelial Cells and the Tumor MicroenvironmentP01CA098101 · NCI · UNIVERSITY OF PENNSYLVANIA · PI RUSTGI, ANIL K · 2003 to 2023
$31.7MWeight loss-induced Microbiome and Adipokine Changes in Barrett's EsophagusU54CA163004 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ABRAMS, JULIAN, RUSTGI, ANIL K · 2011 to 2022
$12.5MUNIVERSITY OF PENNSYLVANIA TRAINING IN GASTROENTEROLOGYT32DK007066 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI JONATHAN P KATZ · 1986 to 2026
$11.7MAutophagy and esophageal tissue remodeling in EoER01DK114436 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI NAKAGAWA, HIROSHI · 2017 to 2024
$3.1MAldh2 and mitochondrial homeostasis in esophageal pathobiologyR01AA026297 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI Hiroshi Nakagawa · 2018 to 2026
$2.9MCYP2E1 Mediated Mitochondrial Injury and Cell Damage in Alcohol Liver DiseaseR01AA022986 · NIAAA · UNIVERSITY OF PENNSYLVANIA · PI AVADHANI, NARAYAN G, KALYANARAMAN, BALARAMAN · 2015 to 2019
$2.6MJARID1B-mediated epigenetic regulation of oncogenic signals in oral cancerR01DE027185 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BASU, DEVRAJ · 2018 to 2021
$1.5MLysyl oxidase mediated fibrosis in eosinophilic esophagitisK08DK106444 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI MUIR, AMANDA BROOKE · 2015 to 2019
$778kThe functional role of mitophagy in esophageal cell biologyK01DK103953 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI WHELAN, KELLY A · 2015 to 2019
$637kJARID1B-mediated epigenetic regulation of oncogenic signals in oral cancerR56DE027185 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BASU, DEVRAJ · 2017 to 2017
$362kNCI NIH HHS F31 CA174176NCI NIH HHS P01 CA098101NCI NIH HHS U54 CA163004NIAAA NIH HHS R01 AA022986NIAAA NIH HHS R01 AA026297NIDCR NIH HHS R01 DE027185NIDCR NIH HHS R56 DE027185NIDDK NIH HHS K01 DK103953NIDDK NIH HHS K08 DK106444NIDDK NIH HHS P30 DK050306NIDDK NIH HHS R01 DK114436NIDDK NIH HHS T32 DK007066NIEHS NIH HHS P30 ES013508
Abstract
Background & Aims: Oropharyngeal and esophageal squamous cell carcinomas, especially the latter, are a lethal disease, featuring intratumoral cancer cell heterogeneity and therapy resistance. To facilitate cancer therapy in personalized medicine, three-dimensional (3D) organoids may be useful for functional characterization of cancer cells Methods: We generated 3D organoids from paired biopsies representing tumors and adjacent normal mucosa from therapy-naïve patients and cell lines. We evaluated growth and structures of 3D organoids treated with 5-fluorouracil Results: Tumor-derived 3D organoids were grown successfully from 15 out of 21 patients (71.4%) and passaged with recapitulation of the histopathology of the original tumors. Successful formation of tumor-derived 3D organoids was associated significantly with poor response to presurgical neoadjuvant chemotherapy or chemoradiation therapy in informative patients ( Conclusions: The single cell-based 3D organoid system may serve as a highly efficient platform to explore cancer therapeutics and therapy resistance mechanisms in conjunction with morphological and functional assays with implications for translation in personalized medicine.
Indexed as
Drug Resistance, NeoplasmAnimalsAutophagyBiopsyCarcinoma, Squamous CellCell Line, TumorChemoradiotherapyEndoscopyEsophageal NeoplasmsFluorouracilHumansHyaluronan ReceptorsMiceOrganoidsOropharyngeal NeoplasmsFluorouracilHyaluronan Receptors3D, 3-dimensional3D Organoids5-Fluorouracil5FU, 5-fluorouracilAutophagyAV, autophagy vesicleCD44CD44H, high expression of CD44CQ, chloroquineDMEM, Dulbecco’s modified Eagle mediumEMT, epithelial-mesenchymal transitionESCC, esophageal squamous cell carcinomaFBS, fetal bovine serumH&E, hematoxylin and eosinIC50, half maximal inhibitory concentrationIHC, immunohistochemistryLC3, light chain 3OPSCC, oropharyngeal squamous cell carcinomaPI, propidium iodideSCCs, squamous cell carcinomasTE11R, 5-fluorouracil–resistant derivative of TE11
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