4.7 Article

Understanding the cellular origin and progression of esophageal cancer using esophageal organoids

Journal

CANCER LETTERS
Volume 509, Issue -, Pages 39-52

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.03.031

Keywords

3D organoids; Esophageal adenocarcinoma; Esophageal squamous cell carcinoma; Esophageal stem cells

Categories

Funding

  1. National Institutes of Health (NIH) [P01CA098101, U54CA163004, R01DK114436, R01AA026297, P30CA013696]
  2. Thoracic Surgery Foundation/Women in Thoracic Surgery
  3. Eleanor and Miles Shore Fellowship from Harvard Medical School/MGH

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Three-dimensional organoids are a novel tool for modeling epithelial cell biology and diseases in the esophagus. Studies using organoids have provided insights into the identification of esophageal cancer stem cells and potential ways to halt malignant progression. Patient-derived organoids offer a platform for personalized medicine research, with future directions including high-throughput genomic screening and study of tumor-microenvironment interactions.
Three-dimensional (3D) organoids are a novel tool to model epithelial cell biology and human diseases of the esophagus. 3D organoid culture systems have been utilized to investigate the pathobiology of esophageal cancer, including both squamous cell carcinoma and adenocarcinoma. Additional organoid-based approaches for study of esophageal development and benign esophageal diseases have provided key insights into esophageal keratinocyte differentiation and mucosal regeneration. These investigations have implications for the identification of esophageal cancer stem cells, as well as the potential to halt malignant progression through induction of differentiation pathways. Patient-derived organoids (PDOs) from human tissue samples allow for unique and faithful in vitro modeling of esophageal cancers, and provide an exciting platform for investigation into personalized medicine and targeted treatment approaches, as well as new models for understanding therapy resistance and recurrent disease. Future directions include high-throughput genomic screening using PDOs, and study of tumor-microenvironmental interactions through co-culture with immune and stromal cells and novel extracellular matrix complexes.

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