Multicellular Modelling of Difficult-to-Treat Gastrointestinal Cancers: Current Possibilities and Challenges |
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Authors: | Sarah K. Hakuno Ellis Michiels Eleonore B. Kuhlemaijer Ilse Rooman Lukas J. A. C. Hawinkels Marije Slingerland |
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Affiliation: | 1.Department of Gastroenterology and Hepatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; (S.K.H.); (E.B.K.);2.InnoSer Belgium NV, 3590 Diepenbeek, Belgium;3.Department of Medical and Molecular Oncology, Free University Brussels, 1090 Brussels, Belgium;4.Department of Medical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; |
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Abstract: | Cancers affecting the gastrointestinal system are highly prevalent and their incidence is still increasing. Among them, gastric and pancreatic cancers have a dismal prognosis (survival of 5–20%) and are defined as difficult-to-treat cancers. This reflects the urge for novel therapeutic targets and aims for personalised therapies. As a prerequisite for identifying targets and test therapeutic interventions, the development of well-established, translational and reliable preclinical research models is instrumental. This review discusses the development, advantages and limitations of both patient-derived organoids (PDO) and patient-derived xenografts (PDX) for gastric and pancreatic ductal adenocarcinoma (PDAC). First and next generation multicellular PDO/PDX models are believed to faithfully generate a patient-specific avatar in a preclinical setting, opening novel therapeutic directions for these difficult-to-treat cancers. Excitingly, future opportunities such as PDO co-cultures with immune or stromal cells, organoid-on-a-chip models and humanised PDXs are the basis of a completely new area, offering close-to-human models. These tools can be exploited to understand cancer heterogeneity, which is indispensable to pave the way towards more tumour-specific therapies and, with that, better survival for patients. |
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Keywords: | patient-derived models patient-derived organoids patient-derived xenografts gastric cancer pancreatic cancer multicellular models tumour modelling co-cultures humanised mice tumour microenvironment |
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