S2515
Radiobiology – DNA damage repair
ESTRO 2026
Category: Radiobiology: DNA damage repair
AZD1390, 5 µM M4076), or an ATRi (50 nM BAY- 1895344, 1.5 µM VE-822) with or without IR. Afterwards, we tested the triple combination of LU, IR, and one of the ATMi/ATRi. We determined apoptosis/necrosis (Annexin V/7-AAD) and cell cycle distribution (Hoechst) with flow cytometry. Moreover, we determined clonogenicity (colony formation assay) and migration (scratch assay). Results: LU alone significantly induced G2/M arrest in all cell lines tested and apoptosis/necrosis in all but one cell line (p=0.029). However, there was no radiosensitization regarding apoptosis/necrosis when a single dose of 2 Gy or 3 Gy or a fractionated dose of 3x 2 Gy or 2x 3 Gy was applied. Regarding clonogenicity, radiosensitization was detectable in a cell line specific manner (SW-872, TE-671). All ATMi and ATRi tested caused a radiosensitizing trend in apoptosis/necrosis analysis when a single dose of 2 Gy IR was applied. A significant induction (p=0.029) was detectable for AZD1390, SW-872, TE-671/BAY-1895344, SW-684, SW-872, TE-671/M4076, SW-872, TE-671/VE- 822, SW-684, SW-872, TE-671. Moreover, AZD1390 and M4076 facilitated a G2/M arrest, which indicates radiosensitizing potential. In preliminary experiments, the triple combination led to an increased amount of apoptosis/necrosis compared to LU+2 Gy in all cell lines and with all inhibitors except for VE-822 in SW- 982 and TE-671. Conclusion: Tough Lurbinectedin alone is cytotoxic in STS cell lines and induces cell cycle arrest, its radiosensitizing effect is limited. However, the additional use of ATMi or ATRi showed radiosensitizing effects. It is necessary to further characterize the single ATMi and ATRi in different STS cell lines and with different fractionation schemes to define the most useful therapeutic for the triple combination with LU and IR. Keywords: soft tissue sarcoma, Lurbinectedin, ATMi/ATRi Mutational Landscape of MLH1-Deficient Colorectal Tissues and Impact of Ionizing Radiation: 3D Organoid-Based Whole Genome Sequencing Analysis JUNG BIN PARK 1,2 , Jeongjae Lee 3 , Min Ji Kim 2,4 , Jeonghwan Youk 5 , Tae Gen Son 6 , Seon Jeong Choi 6 , Kyung Su Kim 1,2 , Eui Kyu Chie 1,2 1 Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea, Republic of. 2 Radiation Oncology, Seoul National University Hospital, Seoul, Korea, Republic of. 3 Internal Medicine, Seoul National University Cancer Research Institute, Seoul, Korea, Republic of. 4 Radiation Oncology, Seoul National Digital Poster Highlight 1191
Digital Poster 346 Low-Dose Imaging Pre-Radiotherapy Alters DNA Repair Kinetics: Radiobiological Insights for Adaptive Radiotherapy Optimization Rana El-Hassan 1 , Aya Zebiane 1 , Leen Katmawi Sabbagh 1 , Charbel Feghaly 2 , Hanine Bou Hadir 2 , Rafka Challita 1 , Toufic Eid 2 , Wassim Abou-Kheir 1 , Larry Bodgi 2,1 1 Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon. 2 Radiation Oncology, American University of Beirut Medical Center, Beirut, Lebanon
Digital Poster 625
Comparison of four ATM or ATR inhibitors for the triple combination with Lurbinectedin and ionizing radiation in soft tissue sarcoma cell lines Laura S. Hildebrand, Hannah Alsheimer, Marius Michel, Orsolya Bodor, Paula Schiller, Felix Grabenbauer, Sabine Semrau, Stefanie Corradini, Luitpold V. Distel Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander- Universität Erlangen-Nürnberg (FAU), Erlangen, Germany Purpose/Objective: Soft tissue sarcoma (STS) is a heterogenous group of malignant diseases classified in various subtypes differing in their prognosis. Our goal was to achieve their radiosensitization with a novel treatment scheme; therefore, we combined the chemotherapeutic Lurbinectedin (LU) with ionizing radiation (IR) and Ataxia telangiectasia mutated (ATM) or Ataxia-telangiectasia and Rad3-related (ATR) inhibition in STS cell lines. Material/Methods: Initially, we treated four STS cell lines (SW-684, SW-872, SW-982, TE-671) with LU (0.5 nM), an ATMi (0.7 µM
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