ESTRO 2025 - Abstract Book

S4018

Radiobiology - Tumour radiobiology

ESTRO 2025

Results: The IHC analyses revealed that deregulated (high or low) nuclear Oct4 protein expression was associated with better LCR compared to intermediate Oct4 expression (p=0.015). A combination of RT with olaparib induced synthetic lethality in Oct4-knockout HNSCC cells. ChIP analysis revealed that DNA repair genes RAD54L, PSMC3IP, and CHEK1 are the Oct4 targets. The siRNA-mediated silencing of Oct4 and MYC resulted in the downregulation of RAD54L and PSMC3IP expression. The genetic knockdown of PSMC3IP and RAD54L led to tumor cell radiosensitization. RAD54L and PSMC3IP knockdown sensitized cells to the combination of olaparib and RT compared to controls. The retrospective IHC analyses demonstrated that similar to the results of the Oct4 IHC analysis, both very high and very low levels of RAD54L and MYC expression are associated with better patient prognosis compared to intermediate levels (p=0.03).

Conclusion: Our study suggests that deregulated expression of Oct4, MYC, and their target genes, such as RAD54L and PSMC3IP, are associated with abnormal HR-mediated DNA repair. It can be used to predict high tumor sensitivity to DNA damaging treatment such as radio(chemo)therapy in patients with HPV-negative HNSCC and to exploit therapeutic approaches based on synthetic lethality through targeting tumor DNA repair pathways (e.g., by PARP inhibition) in combination with RT.

Keywords: HNSCC, DNA repair, stemness

4043

Digital Poster Evaluation of biocompatible gold/silver nanoparticles as radiosensitizers in a prostate cancer model Maria A Lacavalla 1,2 , Sara Cazzola 1 , Federica Vurro 2 , Lisa Alborghetti 2 , Stefano Pizzardi 2 , Antonello E Spinelli 2 , Vincenzo Amendola 1 1 Department of Chemical Sciences, University of Padova, Padova, Italy. 2 Experimental Imaging Centre, IRCCS San Raffaele Scientific Institute, Milan, Italy Purpose/Objective: X-ray radiotherapy (XRT) is a key tumor treatment due to its non-invasiveness and long term efficacy. However, normal tissue toxicity induced by RT treatment remains a challenge. Using radiosensitizing nanoparticles (NPs) could improve XRT efficacy by selectively increasing the dose to the tumor. Moreover, bimetallic NPs have been shown to act as X ray computed tomography (CT) or MRI contrast agents 1,2 . With the aim to expand the current RT and imaging guidance approaches, we evaluated the biocompatibility and radiosensitizing effect of two formulations of NPs through in vitro tests. In vivo experiments were conducted to assess the potential of these NPs as contrast agents for CT and to further demonstrate their degradation over time compared to benchmark contrast agents Material/Methods: Fibroblasts and prostate cancer cells (PC3) were incubated for 48 hours with increasing concentrations of two formulations of gold-silver (AuAg H 2 O+H 2 O 2 and AuAg EtOH) NPs to assess their cytotoxicity. In clonogenic assays for XRT, PC3 cells were treated with 75 µg/mL of NPs for 48 hours and irradiated at different doses. Then, cells were re-plated and allowed to form colonies which were stained to calculate the survival fraction. For in vivo biodistribution studies, Balb/c mice were injected intravenously with the two NPs at a dose of 160 mg Au/kg. CT imaging was performed at different time points post-injection using a small animal CT system. CT image analysis is performed by calculating the mean HU value on regions of interest (ROI) placed over major organs