ESTRO 2025 - Abstract Book

S3995

Radiobiology - Tumour radiobiology

ESTRO 2025

or develop resistance during treatment, reducing its efficacy. In this scenario, the lack of biomarkers that can predict and/or monitor tumor response to radiation represents an urgent clinical need. Previous translational study on selected BC patients treated with pre-operative robotic radiosurgery (pr-RS) highlights the orphan gene Coiled-coil domain containing 97 (CCDC97) as the top differentially expressed hit between patients who better benefit in terms of clinical downstaging from 21Gy single dose pr-RS and those patients whose pTNM remain unchanged after pr-RS. Since little is known about this uncharacterized gene, other than its predicted involvement in DNA damage response via the interaction with SF3b complex, we started to investigate the role of CCDC97 in RT context. Material/Methods: Proteins and gene expression analyses by Western blot and RT-PCR respectively were performed on ER+/HER2- BC cell lines MCF7 and T47 compared to TNBC cell line MDA-MB231. Moreover, phenotypic and/or functional analyses (i. e. cell survival and reactive oxygen species (ROS) production) were conducted in in vitro models after transient silencing using specific siRNA targeting CCDC97 in combination with RT. Results: Firstly, we observed a constitutive expression of CCDC97 in a panel of ER+ BC cell lines when compared to MDA MB231. To point out CCDC97 role in our models, we performed transient CCDC97 silencing and we observed an increase in phospho-γH2AX levels, indicating the induction of DNA damage, paralleled by a significant reduction in cell survival. These effects are certainly increased in combination with RT, suggesting that siCCDC97 may potentiate RT effects. Moreover, we observed a time- and dose-dependent regulation of RAD51 after siCCD97 alone and in combination with RT. Finally, preliminary data indicate that siCCDC97 BC cells exhibit a higher endogenous ROS production compared to non-silenced cells, suggesting either a DNA-direct mechanism by which CCDC97 can enhance RT response and the possibility to cause ferroptotic cell death by increasing lipid peroxidation, thus favouring RT detrimental effects. Conclusion: Collectively, our data suggest that CCDC97 is involved in DNA damage regulation and its role and/or modulation should be further investigated in context of RT response monitoring.

Keywords: CCDC97, radiotherapy response, biomarkers

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Digital Poster Genomic Profiling In Radioresistant Bladder Cancer Cell Lines Taha Lodhi 1,2 , Matej Bartak 1 , Conrado Guerrero Quiles 1 , Vanesa Biolatti 1 , Emilia Powell 1 , Peter Hoskin 1,2,3 , Catharine West 1 , Ananya Choudhury 1,2 1 Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 2 Clinical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom. 3 Clinical Oncology, Mount Vernon Cancer Centre, Northwood, United Kingdom Purpose/Objective: Muscle-invasive bladder cancer (MIBC) has high recurrence rates after radiotherapy, often due to radioresistance. No clinical biomarkers can identify patients at risk of recurrence. The lack of MIBC radioresistance models limits progress in identifying resistance mechanisms and biomarkers. This project aimed to develop and use in vitro models to characterise the radioresistance mechanisms in MIBC, identifying novel radiosensitivity biomarkers.