Radiation response assessment of organoids derived from patients with pancreatic cancer

• Published in: Clinical and translational radiation oncology 2024-09, Vol.48, p.100829, Article 100829
• Main Authors: van Goor, Iris W.J.M., Raymakers, Leon, Andel, Daan S.H., Brosens, Lodewijk A.A., Kranenburg, Onno, Leusen, Jeanette H.W., Meijer, Gert J., Molenaar, I. Quintus, van Santvoort, Hjalmar C., de Vries, J.H. Wilfred, Wopereis, Andre J.M., Intven, Martijn P.W., Daamen, Lois A.
• Format: Article
• Language: English
• Subjects: Dose–response correlation; Original; Pancreatic ductal adenocarcinoma; Patient derived organoids; Radiation; Radiotherapy; Response; Sensitivity
• ISSN: 2405-6308; 2405-6308
• DOI: 10.1016/j.ctro.2024.100829

•Pancreatic cancer patient derived organoids (PDOs) can model radiation response.•Both PDOs were sensitive to irradiation, although heterogeneity in response was found.•Sufficient time until readout (i.e., 10 days) is crucial for proper evaluation of results. The effectiveness of radiotherapy for pancreatic cancer is debated. Patient-derived organoids (PDOs) already mimicked clinical radiation response in other cancer types, which could be valuable in pancreatic cancer as well. This study aimed to investigate whether PDOs can be used to model RT response in pancreatic cancer and to explore the presence of a dose–response correlation. PDOs derived from two pancreatic cancer patients (HUB-08-B2-022A and HUB-08-B2-026B) were irradiated with doses ranging from 0 to 40 Gray. Viability assessments were conducted after seven and 10 days by measuring ATP-levels. Results were normalized, defining the viability at 0 Gray as 100 % and an absolute viability of 0 as 0 %. The relative area under the curve (rAUC) was calculated (0 = total sensitivity, 1 = total resistance). With a readout time of seven days, both HUB-08-B2-022A and HUB-08-B2-026B exhibited viability above 50 % at the highest dose of 12 Gy (rAUC of 0.79 and 0.69, respectively). With a readout time of 10 days, both PDOs showed a dose–response relation although HUB-08-B2-022A was more sensitive than HUB-08-B2-026B (rAUC of 0.37 and 0.51, respectively). Increasing the radiation dose to 40 Gy did not further affect viability, but the dose–response relation remained present (rAUC of 0.13 and 0.26, respectively). In the final experiment with a readout time of 10 days and a maximum dose of 14 Gy, the dose–response correlation was paramount in both PDOs (rAUC 0.28 and 0.45, respectively), with HUB-08-B2-022A being most sensitive. In this setup, both pancreatic cancer PDOs showed an irradiation dose–response correlation. These preliminary findings suggest that pancreatic cancer PDOs are suitable for assessing radiation response in vitro. Further experiments are needed to eventually simulate treatment responses to personalized treatment strategies.