ESTRO 2024 - Abstract Book

S5325

Radiobiology - Tumour biology

ESTRO 2024

In 2D experiments, the dose regimen did not alter the amount of DLD-1 and HCT116 cells undergoing ferroptosis after RT. However, in HT29 and CT26 the percentage of cells going into ferroptosis increased under fractionated radiation. The cellular fraction in apoptosis and necroptosis after RT remained consistent for DLD-1 and HCT116 regardless of the dose regimen, while HT29 displayed a decreased fraction undergoing apoptosis and an increased percentage of necroptosis. Fractionated radiation had the opposite effect on the necroptosis and apoptosis levels in CT26 (Table 1). A hypoxic environment reduced the fraction of DLD-1 and HT29 cells going into ferroptosis, while ferroptosis percentages remained similar in CT26. In contrast, the levels of ferroptosis in HCT116 elevated under low oxygen levels. No apparent trend was observed for apoptosis and necroptosis (table 1). The levels of RT-induced RCD are drastically lower in HCT116 (30%) compared to DLD-1 (50%). Prompting an evident correlation between the pronounced effect of SSZ in DLD-1 and its vulnerability to FINs. To confirm these results, 3D experiments were performed. Preliminary data suggest that ferroptosis is the most important type of RT-induced RCD in DLD-1 spheroids, while ferroptosis is of similar importance to apoptosis and necroptosis in HT29, HCT116 and CT26 spheroids. In vivo experiments are ongoing. Lastly, the contribution of ferroptosis in normal tissue toxicity was evaluated in vitro . Preliminary data suggest that SSZ treatment increased the ROS levels in HIEC6 cells (fold change up to 2.4). Additionally, increased amounts of lipid peroxidation were observed in SSZ-treated HIEC6 cells to a similar extent as in CRC cells (up to 2.3 fold).

Conclusion:

FINs exhibit promising potential as radiosensitizers in CRC. However, the significance of ferroptosis in RT-induced RCD is ambiguous. This study underscores that distinct CRC cell lines contain heterogeneous ferroptosis sensitivities emphasizing the importance of extensive research into predictive biomarkers for ferroptosis vulnerability. Moreover,