ESTRO 2024 - Abstract Book

S5355

Radiobiology - Tumour biology

ESTRO 2024

substantiated by a significant reduction of 47 to 70% in the amount /intensity of yH2AX ( 0.5h post-irradiation) and 53BP1 (24h post-irradiation) foci after irradiation in the presence of the ATM and ATR inhibitors (Fig. 2), indicating a potent and long term inhibition of DNA repair. Of note, data with PARP inhibitor will follow. The same effect is observed on Western Blot where the levels of phosphorylated downstream proteins yH2AX and CHK2 of the ATM pathway decrease after treatment with inhibitor. To start unravelling the impact of the inhibitors on activation of the cGAS-STING pathway in the tumor cells, we first showed the presence of the pathway in the three cell lines using qPCR. The cGAS-STING pathway can be activated in PC3 and DU145 cells by herring testis (HT)-DNA and irradiation, as confirmed by increased phosphorylated STING. Furthermore, irradiation in combination with ATM inhibition leads to increased STING phosphorylation in DU145 cells.