Title: Abstract 44: Assessment of pancreatic cancer 3D organotypic cultures as models for functional preclinical analysis
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the deadliest of all cancers, with a five-year survival rate of 8%. Decades of research has done little to improve patient outcomes. To identify key therapeutic strategies, appropriate research preclinical models are critical for testing the efficacy of drugs or downstream functional genomic analysis. Current methods of growing PDAC established cell lines in a 2D monolayer do not fully represent how the tumor cells grow in vivo as they fail to recapitulate the physiology of tumors in vivo due to different architecture, adherence structures and biochemical gradients. Patient-derived xenografts can retain the histological and genetic characteristics of their donor tumor and can remain stable across passages. Three-dimensional (3D) organoids grown ex vivo are tractable also retain the architecture, genotype and phenotype of a patients' tumor.However, a detailed comparative assessment of the utility of organoids, matched 2D cell lines and 3D cell organotypic models to assess the complex biology, interactions, response to therapeutic regimens has not been performed.Using our unique protocol, we have established PDAC organoids and isogenetically matched 2D cell lines derived from PDAC PDX tumors. To establish if these matched 2D cell lines grown in 3D can recapitulate the organoid model, we cultured the matched cell lines in 3D organoid media in non-adherent, Matrigel containing cultures. The expression of PDAC histological markers between the original tumor, the PDX tumor, organoid and matched cell line in 3D and 2D has identified differential expression of tumor initiating cell (TIC) markers. RNA-seq transcriptomics of the 2D cell line models, matched recapitulated 3D organotypic models, organoids, PDX-tumor and patient tumor will reveal the application of these models for ex vivo downstream functional analysis.Citation Format: Shannon R. Nelson, Sandra Roche, Fiona O'Neill, AnneMarie Larkin, John Crown, Naomi Walsh. Assessment of pancreatic cancer 3D organotypic cultures as models for functional preclinical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 44.