S2629
Radiobiology - Tumour radiobiology
ESTRO 2026
upregulated in aPTV cells and played a key role in enhancing radiation-induced cell survival. ARPC2 knockout resulted in significant cell cycle arrest, reduced proliferation, and increased apoptosis in vitro. In xenograft model, ARPC2 KO tumors displayed significantly reduced growth and heightened radiosensitivity compared to scramble controls. Post- radiation tumor burden was markedly decreased in ARPC2-deficient xenografts. Conclusion: Our study identifies ARPC2 as a critical driver of radioresistance and tumor growth in high-grade glioma. ARPC2 expression correlates with inadequate response to RT despite optimal PTV coverage, highlighting its potential utility as a predictive biomarker and therapeutic target. Pharmacologic inhibition of ARPC2 may sensitize radioresistant glioma subtypes to RT, representing a promising avenue for precision oncology in HGG management. Keywords: Radioresistant glioma 、 ARPC2 、 CRISPR/Cas9 FLASH-radiotherapy elicits distinct ferroptotic responses in colorectal cancer and intestinal epithelial cells. Lisa Kerkhove 1,2 , Inès Dufait 2,1 , Febe Geirnaert 1,2 , Racell Nabha 2 , Iris Apale 2 , Dorien De Ridder 3 , Pierre Montay- Gruel 4,5 , Thierry Gevaert 1,2 , Mark De Ridder 1,2 1 Research Centre for Digital Medicine, Vrije Universiteit Brussel, Brussels, Belgium. 2 Radiotherapy, UZ Brussel, Brussels, Belgium. 3 Dermatology, UZ Brussel, Brussels, Belgium. 4 Radiation Oncology, Iridium Netwerk, Antwerp, Belgium. 5 Antwerp Research in Radiation Oncology (AreRO), Centre for Oncological Research (CORE), University of Antwerp, Antwerp, Belgium Purpose/Objective: FLASH, or ultra-high dose rate radiotherapy (RT), is reshaping the field of oncology. It offers sparing of normal tissues from radiation-induced side effects while maintaining effective tumour control, a phenomenon known as the FLASH effect. Although the Digital Poster 1040 underlying mechanisms remain unclear, previous studies have observed reduced lipid peroxidation following FLASH-RT in micelles and liposomes1,2, suggesting a possible role for ferroptosis, an iron- dependent type of cell death driven by the accumulation of lipid peroxides3. This study investigated whether FLASH-RT induces ferroptosis in human colorectal cancer cells (CRC) and human intestinal epithelial cells (HIEC). Material/Methods: Two human cell lines, DLD-1 (CRC) and HIEC6 (intestinal epithelial cells) were irradiated with 10Gy
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ARPC2 Drives Radioresistance and Tumor Persistence in High-Grade Glioma Under Suboptimal Radiotherapy Coverage Jang-Chun Lin 1,2 , Jeng-Fong Chiou 3,2 , Hsing-Lung Chao 4 , Jo-Ting Tsai 1,2 , Wei-Hsiu Liu 5 , Chia-Hwa Lee 6 1 Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan. 2 Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 3 Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan. 4 Department of Radiation Oncology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 5 Department of Neurological Surgery, Tri-Service General Hospital and National Defense Medical University, Taipei, Taiwan. 6 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan Purpose/Objective: High-grade glioma (HGG) is a highly malignant brain tumor for which radiotherapy (RT) remains a cornerstone of adjuvant treatment. Despite aggressive multimodal approaches, HGG frequently recurs locally, particularly in regions with suboptimal RT dosing. A clinically effective RT plan requires ≥ 95% coverage of the planning target volume (PTV); however, this threshold is not always met in real-world clinical settings. This study aims to identify key molecular mediators that modulate HGG prognosis and RT sensitivity, with a view toward advancing precision radiotherapy strategies. Material/Methods: We retrospectively analyzed the relationship between PTV coverage and survival in 50 patients with HGG through TCGA GSE81934 dataset. Two patient-derived primary glioma cell lines were established: HGG-1 (from patients with adequate PTV coverage, aPTV >95%) and HGG-2 (from patients with inadequate PTV coverage, nPTV <95%). Actin-related protein 2/3 complex subunit 2 (ARPC2) is likely to be a important participant in tumor invasion and migration. Transcriptomic comparison identified ARPC2 as a differentially expressed gene enriched in the aPTV group. CRISPR/Cas9-mediated knockout (KO) of ARPC2 was performed in HGG-1 cells. Functional validation was conducted through in vitro assays and in vivo studies using a SCID mouse xenograft model, followed by targeted cranial irradiation. Results: HGG-1 cells exhibited greater radio resistance compared to HGG-2 cells, suggesting intrinsic molecular adaptations that promote survival under therapeutic irradiation. Integrative data mining and functional assays revealed that ARPC2 was
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