The application of pancreatic cancer organoids for novel drug discovery

Expert Opin Drug Discov. 2023 Apr;18(4):429-444. doi: 10.1080/17460441.2023.2194627. Epub 2023 Mar 26.

Abstract

Introduction: Pancreatic ductal adenocarcinoma presents with a dismal prognosis. Personalized therapy is urgently warranted to overcome the treatment limitations of the 'one-size-fits-all' scheme. Organoids have emerged as fundamental novel tools to study tumor biology and heterogeneity, hence overcoming limitations of other model systems by better-reflecting tissue heterogeneity and recapitulating in-vivo processes. Besides their crucial role in basic research, they have evolved as tools for translational drug discovery and patient stratification.

Areas covered: This review highlights the achievements of an organoid-based drug investigation and discovery. The authors present an overview of studies using organoids for drug testing. Further, they pinpoint studies correlating the in vitro prediction of organoids to the actual patient`s response. Furthermore, the authors describe novel model systems and take a thorough overlook of microfluidic chips, synthetic matrices, multicellular systems, bioprinting, and stem cell-derived pancreatic organoid systems.

Expert opinion: Organoid systems promise great potential for future clinical applications. Indeed, they may be implemented into informed decision-making for guiding therapies. However, validation by randomized trials is mandatory. Additionally, organoids in combination with other cellular compartments may be exploited for drug discovery by studying niche-tumor interaction. Yet, several precautions must be kept in mind, such as standardization and reproducibility.

Keywords: assembloids; drug discovery; microfluidic chips; multicellular systems; organoids; pancreatic cancer; personalized medicine.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Discovery
  • Humans
  • Organoids*
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology
  • Reproducibility of Results