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World J Gastroenterol. Jul 14, 2014; 20(26): 8471-8481
Published online Jul 14, 2014. doi: 10.3748/wjg.v20.i26.8471
Pancreatic cancer organotypics: High throughput, preclinical models for pharmacological agent evaluation
Stacey J Coleman, Jennifer Watt, Prabhu Arumugam, Leonardo Solaini, Elisabeta Carapuca, Mohammed Ghallab, Richard P Grose, Hemant M Kocher
Stacey J Coleman, Jennifer Watt, Prabhu Arumugam, Leonardo Solaini, Elisabeta Carapuca, Mohammed Ghallab, Richard P Grose, Hemant M Kocher, Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom
Jennifer Watt, Prabhu Arumugam, Leonardo Solaini, Hemant M Kocher, Barts and the London HPB Centre, The Royal London Hospital, Barts Health NHS Trust, London EC1M 6BQ, United Kingdom
Author contributions: Coleman SJ designed and wrote the paper; Watt J, Arumugam P, Solaini L, Carapuca E, Ghallab M and Grose RP contributed equally to the writing of the paper; Kocher HM made final amendments of the paper and approval of the version to be published.
Correspondence to: Hemant M Kocher, MS, MD, FRCS, Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom. h.kocher@qmul.ac.uk
Telephone: +44-20-78823579 Fax: +44-20-78823884
Received: October 18, 2013
Revised: January 15, 2014
Accepted: April 1, 2014
Published online: July 14, 2014
Abstract

Pancreatic cancer carries a terrible prognosis, as the fourth most common cause of cancer death in the Western world. There is clearly a need for new therapies to treat this disease. One of the reasons no effective treatment has been developed in the past decade may in part, be explained by the diverse influences exerted by the tumour microenvironment. The tumour stroma cross-talk in pancreatic cancer can influence chemotherapy delivery and response rate. Thus, appropriate preclinical in vitro models which can bridge simple 2D in vitro cell based assays and complex in vivo models are required to understand the biology of pancreatic cancer. Here we discuss the evolution of 3D organotypic models, which recapitulare the morphological and functional features of pancreatic ductal adenocarcinoma (PDAC). Organotypic cultures are a valid high throughput preclinical in vitro model that maybe a useful tool to help establish new therapies for PDAC. A huge advantage of the organotypic model system is that any component of the model can be easily modulated in a short time-frame. This allows new therapies that can target the cancer, the stromal compartment or both to be tested in a model that mirrors the in vivo situation. A major challenge for the future is to expand the cellular composition of the organotypic model to further develop a system that mimics the PDAC environment more precisely. We discuss how this challenge is being met to increase our understanding of this terrible disease and develop novel therapies that can improve the prognosis for patients.

Keywords: 3D organotypic model, Pancreatic cancer, Pancreatic stellate cell, Stroma, Preclinical models

Core tip: Pancreatic cancer carries a terrible prognosis, as the fourth most common cause of cancer death in the Western world. One of the reasons no effective treatment has been developed in the past decade may in part, be explained by the influences exerted by the tumour microenvironment. The tumour stroma cross-talk in pancreatic cancer can influence chemotherapy delivery and response rate. Organotypic models of pancreatic cancer allow new therapies that can target the cancer, the stromal compartment or both to be tested in a model that mirrors the in vivo situation and can help improve patient prognosis.