The Diverse Applications of Pancreatic Ductal Adenocarcinoma Organoids

The Diverse Applications of Pancreatic Ductal Adenocarcinoma Organoids

Ronnie Ren Jie Low 1,2,3,Wei Wen Lim 3,Paul M. Nguyen 3,Belinda Lee 1,2,Michael Christie 1,2,Antony W. Burgess 1,2,Peter Gibbs 1,2,4,Sean M. Grimmond 3,5,Frédéric Hollande 3,5 andT racy L. Putoczki 1,2
1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
2 Department of Medical Biology, The University of Melbourne, Melbourne, VIC 3052, Australia
3 Victorian Comprehensive Cancer Centre, University of Melbourne Centre for Cancer Research, Melbourne, VIC 3000, Australia
4 Department of Medical Oncology, Western Health, Melbourne, VIC 3052, Australia
5 Department of Clinical Pathology, University of Melbourne, Melbourne, VIC 3000, Australia

Simple Summary

Patients diagnosed with pancreatic cancer have very few treatment options. In order to identify new treatment opportunities, and develop new drugs for clinical use, appropriate model systems that take into account the complexities of a tumor are required. In this review, we summarize the current and emerging opportunities to accurately model pancreatic cancer using organoid technologies. We highlight the need for continued development of these complex model systems in order to inform personalized treatment.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies. While immortalized cancer cell lines and genetically engineered murine models have increased our understanding of PDAC tumorigenesis, they do not recapitulate inter- and intra-patient heterogeneity. PDAC patient derived organoid (PDO) biobanks have overcome this hurdle, and provide an opportunity for the high throughput screening of potential new therapies. This review provides a summary of the PDAC PDO biobanks established to date, and discusses how they have advanced our understanding of PDAC biology. Looking forward, the development of coculturing techniques for specific immune or stromal cell populations will enable a better understanding of the crosstalk that occurs within the tumor microenvironment, and the impact of this crosstalk on treatment response.