ESTRO 2024 - Abstract Book

S5358

Radiobiology - Tumour biology

ESTRO 2024

Conclusion:

Using our in vitro spheroid model, we compared the effects of Mito-ATO and Mito-PEG-ATO to unmodified ATO on hypoxia attenuation. We showed that Mito-PEG-ATO alleviates hypoxia in both spheroid models and seems more potent than ATO, while Mito-ATO was only able to alleviate hypoxia in MC38 spheroids. The observed dose-dependent reduction in hypoxia in both spheroid models using Mito-PEG-ATO could sensitize hypoxic tumor cells for radiotherapy, immunotherapy and their combination. In addition, Mito-PEG-ATO has improved solubility and selectively accumulates in mitochondria of cancer cells, thereby minimizing the toxic side effects. For these reasons, Mito-PEG-ATO seems a promising OXPHOS inhibitor to alleviate hypoxia with good prospects for clinical translation.