Photo Credit: Dr._Microbe

The following is a summary of “Radiation response assessment of organoids derived from patients with pancreatic cancer,” published in the September 2024 issue of Oncology by Goor et al.

The effectiveness of radiotherapy for pancreatic cancer remains contentious. Patient-derived organoids (PDOs) have previously demonstrated the ability to mimic clinical radiation responses in other cancer types, suggesting potential applicability for pancreatic cancer. This study aimed to investigate the utility of PDOs in modeling radiotherapy (RT) response in pancreatic cancer and to explore the presence of a dose-response correlation.

PDOs derived from two patients with pancreatic cancer (HUB-08-B2-022A and HUB-08-B2-026B) were irradiated with doses ranging from 0 to 40 Gray (Gy). Viability assessments were conducted after seven and 10 days by measuring ATP levels. Results were normalized, defining the viability at 0 Gy as 100% and an absolute viability of 0 as 0%. The relative area under the curve (rAUC) was calculated, with 0 indicating total sensitivity and 1 indicating 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 displayed a dose-response relationship, 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 relationship 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 of 0.28 and 0.45, respectively), with HUB-08-B2-022A being the most sensitive.

Both pancreatic cancer PDOs exhibited a clear irradiation dose-response correlation in this setup. These preliminary findings suggest that pancreatic cancer PDOs are suitable for assessing radiation response in vitro. Further experiments are necessary to fully explore their potential in simulating treatment responses and guiding personalized treatment strategies.

Source: sciencedirect.com/science/article/pii/S240563082400106X