title: Pancreatic cancer organotypics: High throughput, preclinical models for pharmacological agent evaluation.
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.
authors.affiliation: 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.
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Coleman
authors.affiliation: 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.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Watt
authors.affiliation: 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.
authors.forename: Prabhu
authors.initials: P
authors.lastname: Arumugam
authors.affiliation: 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.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Solaini
authors.affiliation: 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.
authors.forename: Elisabeta
authors.initials: E
authors.lastname: Carapuca
authors.affiliation: 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.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Ghallab
authors.affiliation: 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.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Grose
authors.affiliation: 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.
authors.forename: Hemant M
authors.initials: HM
authors.lastname: Kocher
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents
keywords: 3D organotypic model; Pancreatic cancer; Pancreatic stellate cell; Preclinical models; Stroma