S2633
Radiobiology - Tumour radiobiology
ESTRO 2026
1 Department of Radiation Oncology, American University of Beirut, Beirut, Lebanon. 2 Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon Purpose/Objective: Breast cancer is the most commonly diagnosed malignancy in women worldwide, while bladder cancer remains one of the most recurrent urological tumors. Radiotherapy (RT) is a cornerstone treatment for both; however, radioresistance limits its efficacy. Ro 90- 7501, originally developed to inhibit amyloid β 42 fibril formation in Alzheimer’s disease, has recently been shown to enhance radiosensitivity in cervical cancer cells by impairing DNA double-strand break (DSB) repair. This study investigates the potential of Ro 90- 7501 to radiosensitize breast and bladder cancer cells while sparing normal fibroblast. Material/Methods: Two breast (MDA-MB-231, MCF7) and two bladder (UM-UC-5, T24) cancer cell lines, along with a normal fibroblast cell line (GM03652), were treated with Ro 90- 7501 (1, 3 and 10 μ M) before irradiation. DSB repair kinetics were assessed by γ -H2AX and pATM foci quantification using immunofluorescence. The clonogenic assay and the sphere formation assay were performed to assess cellular radiosensitivity. Results: Following 2Gy irradiation, Ro 90-7501 significantly increased residual γ -H2AX foci at 24h in breast and bladder cancer cells (p<0.001), indicating impaired DNA repair (Figure 1-A). A significant reduction in pATM foci was observed at 10min in both cancer cell types (p<0.05), suggesting impaired DNA damage signaling (Figure 1-B). No effect was observed on the normal fibroblast (p>0.05).Ro 90-7501 significantly reduced the surviving fraction of both bladder cancer cells at 1 and 2Gy (p<0.01) across all concentrations. A significant decrease was also observed in MCF7 at 2Gy for 3 and 10 μ M (p< 0.01). No significant effects were detected at higher doses (data not shown) or in normal fibroblasts (p>0.05) (Figure 2-A).In 3D culture, Ro 90-7501 significantly reduced sphere number in MDA-MB-231 alone and in both breast cancer cell lines after 2Gy (p<0.01) (Figure 2-B). Sphere diameter decreased only at 10 μ M, with or without irradiation, in MDA-MB-231 and MCF7 (p<0.01), while no significant effects in sphere number or diameter were observed in bladder cancer cells (p>0.05).
Figure 1: Induction of γ -H2AX (A) and pATM (B) foci by Ro 90-7501 at different concentrations, alone or with radiotherapy, in GM03652, MCF-7, MDA-MB-231, UM- UC-5 and T24. (*: p<0.05, **: p<0.01, ***: p<0.001).
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