S2636
Radiobiology - Tumour radiobiology
ESTRO 2026
Conclusion: A core set of genes is linked to radioresistance, involved in cell-cycle control, oxidative homeostasis and ECM dynamics in both DU145 and TERT-PrEC cells. Despite model heterogeneity, overlapping pathways suggested conserved mechanisms of radiation response. Integration with genomic, in vitro, and locally radiorecurrent clinical datasets is underway to refine and validate predictive biomarkers of radioresistance. References: 1) Shore ND, Moul JW, Pienta KJ, et al. Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification. Prostate Cancer Prostatic Dis. 2024;27:192–201. doi:10.1038/s41391-023-00712-z2) Love, M.I., Huber, W. and Anders, S. (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol, 15, 550. Keywords: Radioresistance, Transcriptomic, Prostate Cancer Identification of increased NQO1 and Keap1 expression in radioresistant pancreatic cancer cells Clara Rebhan 1 , Julian Kapfer 1 , Manuela Feyereisen 1 , Julia Pangerl 1 , Daniela Schilling 1,2 , Omid Azimzadeh 3 , Stephanie E Combs 1,2 , Sophie Dobiasch 1,2 1 Department of Radiation Oncology, Technical University of Munich (TUM), Klinikum rechts der Isar, Munich, Germany. 2 Institute of Radiation Medicine (IRM), Helmholtz Zentrum München, Neuherberg, Germany. 3 Section Radiation Biology, Federal Office for Radiation Protection (BfS), Neuherberg, Germany Purpose/Objective: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal tumor diseases, with a 5-year survival rate of approximately 13%. The poor prognosis is driven by high therapy resistance, aggressive tumor growth and pronounced genetic heterogeneity. Preliminary work showed considerable variability in radiation sensitivity across a panel of 72 murine and 12 human PDAC cell lines. This study aims to identify molecular mechanisms underlying radiation resistance and to explore potential targets for Digital Poster 3666 radiosensitization. Material/Methods: The (phospho-)proteome of murine PDAC cell lines previously classified as radioresistant and radiosensitive was analyzed. Protein expression of NADPH oxidoreductase 1 (NQO1) and its regulator protein Keap1 was investigated in four murine and three human PDAC cell lines using Western blot.
stress (CTRL-R2), apoptotic/protein-stress (CTRL-R3), metabolic (MYC), and cell-cycle (P53MYC) pathways. Across models, 103 DEGs overlapped in DU145 and 99 in TERT-PrEC, with SV2A, DCLK2, and CRACDL shared between model systems, implicating genes involved in vesicle trafficking, neuronal remodelling, and cytoskeletal regulation. Co-expression analyses revealed discrete gene modules significantly correlated with radioresistance, each represented by a hub gene and dominant enriched pathway, highlighting coordinated transcriptional networks linked to structural remodelling, metabolic adaptation, and proliferative control (Figure 1). Filtering for consistent expression yielded 21 DU145 and 11 TERT- PrEC core resistance genes. Network mapping of these defined clusters, linked to ECM organisation, oxidative stress, mitotic regulation, and intracellular signalling (Figure 2).
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