Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

Science. 2018 Feb 23;359(6378):920-926. doi: 10.1126/science.aao2774.

Abstract

Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm*
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / pathology
  • Genomics
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Organoids / drug effects*
  • Organoids / metabolism
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use
  • Precision Medicine / methods*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • regorafenib