Poster Presentation 37th Lorne Cancer Conference 2025

Modelling pancreatic cancer using organoid co-culture (#248)

Suya Shen 1 2 , Ka Yee Fung 1 , Clara Kosasih 1 , Trinity Peachey 1 , Peter Gibbs 1 3 , Belinda Lee 1 4 5 , Tracy Putoczki 1
  1. Personalised Oncology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  2. Department of Pancreatic and Metabolic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical school, Nanjing University, Nanjing, Jiangsu, China
  3. Department of Medical Oncology, Western Health, Footscray, Victoria, Australia
  4. Northern Health, Epping, Victoria, Australia
  5. Peter MacCallum Cancer Centre, Parkville, Victoria, Australia

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers due to late diagnosis and resistance to chemotherapy. Few treatment options exist for these patients, and chemotherapy is often provided with palliative intent. Pancreatic cancer is highly desmoplastic, with a large proportion of the tumour frequently comprised of stromal cells including fibroblasts and immune cells that shape the tumour microenvironment (TME)1. Creating an in vitro platform to model interactions within the tumour microenvironment, beyond the tumour itself, is crucial for advancing personalized therapy.

 

Patient-derived organoids (PDOs) are mini-replicas of a patient tumour grown in vitro that retain the histological and genetic characteristics of the original tumour2. Once established, PDOs can be expanded and stored as ‘living’ biobanks, making them valuable for cancer research. PDAC organoids have been proven to reflect patient drug responses, making them adaptable for clinical applications3. We established a biobank of patient and mouse pancreatic cancer organoids, as well as fibroblast cell lines and used these to generate a 3D co-culture model. Our results highlight the potential of PDAC co-culture models, not only for drug response profiling to guide diverse standard-of-care therapies for PDAC, but also for further unravelling the role of stromal cells in supporting chemoresistance mechanisms.

 

Reference:

  1. Schuth S, Le Blanc S, Krieger TG, et al. Patient-specific modelling of stroma-mediated chemoresistance of pancreatic cancer using a three-dimensional organoid-fibroblast co-culture system. J Exp Clin Cancer Res. 2022 Oct 22;41(1):312.
  2. Elyada E, Bolisetty M, Tuveson DA, et al. Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts. Cancer Discov. 2019 Aug;9(8):1102-1123.
  3. Öhlund D, Handly-Santana A, Tuveson DA, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017 Mar 6;214(3):579-596