Mar 28, 2020

Pancreatic cancer-derived organoids - a disease modeling tool to predict drug response

United European Gastroenterology Journal
Pierre-Olivier FrappartAlexander Kleger

Abstract

Organotypic cultures derived from pancreatic ductal adenocarcinoma (PDAC) termed pancreatic ductal cancer organoids (PDOs) recapitulate the primary cancer and can be derived from primary or metastatic biopsies. Although isolation and culture of patient-derived pancreatic organoids were established several years ago, pros and cons for individualized medicine have not been comprehensively investigated to date. We conducted a feasibility study, systematically comparing head-to-head patient-derived xenograft tumor (PDX) and PDX-derived organoids by rigorous immunohistochemical and molecular characterization. Subsequently, a drug testing platform was set up and validated in vivo. Patient-derived organoids were investigated as well. First, PDOs faithfully recapitulated the morphology and marker protein expression patterns of the PDXs. Second, quantitative proteomes from the PDX as well as from corresponding organoid cultures showed high concordance. Third, genomic alterations, as assessed by array-based comparative genomic hybridization, revealed similar results in both groups. Fourth, we established a small-scale pharmacotyping platform adjusted to operate in parallel considering potential obstacles such as culture conditions, timin...Continue Reading

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Mentioned in this Paper

Pharmaceutical Preparations
Pdx1 protein, mouse
Pancreatic Ductal Adenocarcinoma
Administration of Antineoplastic Agent
Neoplasm Metastasis
Biopsy
Laboratory Culture
Biological Markers
Array-Based Comparative Genomic Hybridization
Organoids

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