Multicellular modelling of difficult-to-treat gastrointestinal cancers: current possibilities and challenges

Hakuno, S.K.; Michiels, E.; Kuhlemaijer, E.B.; Rooman, I.; Hawinkels, L.J.A.C.; Slingerland, M. (2022)

Article / Letter to editor

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.

• patient-derived models
• patient-derived organoids
• patient-derived xenografts
• gastric cancer
• pancreatic cancer
• multicellular models
• tumour modelling
• co-cultures
• humanised mice
• tumour microenvironment

• All authors: Hakuno, S.K.; Michiels, E.; Kuhlemaijer, E.B.; Rooman, I.; Hawinkels, L.J.A.C.; Slingerland, M.
• Date: 2022-03-01
• Journal: International Journal of Molecular Sciences
• Volume: 23
• Issue: 6
• DOI: doi:10.3390/ijms23063147