A 3D culture model of pancreatic cancer (PDAC)

Version française

In drug discovery traditional 2D cell culture models do not accurately predict the clinical efficacy. Drug discovery traditionally starts with a high-throughput screen using 2D cell culture methods, however when drug candidates from such screens reach preclinical and clinical trials 95% fail [1]. 3D culture of ductal epithelial cells such as those that form PDAC usually involves embedding the cells in extracellular matrix and allowing them to form tubules (figure 1). Gene expression profiles of 3D cultures more accurately match tumours in vivo and thus should yield higher quality hits in drug screens but until recently there were no reliable 3D culture methods for pancreatic cancer cells. Now a 3D alternative to 2D culture of pancreatic cancer cells has been developed that is compatible with high-throughput screening [2].

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Figure 1: Example immunofluorescence image of cells grown in organoid 3D culture. Credit: The Journal of Cell Biology. No changes were made. Creative Commons Attribution-NonCommercial-ShareAlike 2.0 Generic (CC BY-NC-SA 2.0).

A method to generate organoids from endoscopic biopsies of the human pancreas has been developed which allows 3D culture of normal and  pancreatic cancer cells. Moreover these organoids can form xenograft mouse models [2]. The organoids can be cryopreserved and an organoid bank is planned to facilitate research on pancreatic cancer. This new 3D model system should greatly improve hit quality in drug discovery screens for pancreatic cancer.

Refs

  1. Lovitt, Carrie, Todd Shelper, and Vicky Avery. ‘Advanced Cell Culture Techniques for Cancer Drug Discovery’. Biology 3, no. 2 (30 May 2014): 345–67. doi:10.3390/biology3020345.
  2. Boj, Sylvia F., Chang-Il Hwang, Lindsey A. Baker, Iok In Christine Chio, Dannielle D. Engle, Vincenzo Corbo, Myrthe Jager, et al. ‘Organoid Models of Human and Mouse Ductal Pancreatic Cancer’. Cell 160, no. 1–2 (January 2015): 324–38. doi:10.1016/j.cell.2014.12.021.
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