S2573
Radiobiology – Normal tissue radiobiology
ESTRO 2026
driven regeneration. The effect was reversible: TACs promptly resumed proliferation after the transient window with no sustained arrest. Transient CDK4/6 blockade phenocopied these protective effects, supporting a “therapeutic pause” mechanism based on a transient, peri-irradiation shift toward G1.
analysis. Radiotherapy and Oncology 2023; 186.2. Stumpf PK, Cittelly DM, Robin TP, et al. Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4. Clin Cancer Res 2019; 25(13): 3946-53.3. Yu LS, Fan YY, Ye G, et al. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage. Exp Ther Med 2016; 11(3): 709-16. Keywords: Radionecrosis, Trastuzumab Emtansine, Curcumin
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Transient hedgehog pathway suppression mitigates radiotherapy-induced alopecia Shih-fan Lai 1,2 , Sung-Jan Lin 3
1 Radiaiton Oncology, National Taiwan University Cancer Center, Taipei, Taiwan. 2 Oncology, National Taiwan University Hospital, Taipei, Taiwan. 3 Biomedical Engineering, National Taiwan University, Taipei, Taiwan Purpose/Objective: Anagen hair follicles contain rapidly cycling hair-matrix transit-amplifying cells (TACs), making them highly susceptible to radiotherapy-induced genotoxic injury and alopecia. Although continuous Hedgehog (Hh) signaling in TACs is required for anagen maintenance, brief Hh inhibition induces only a transient proliferation arrest. We therefore investigated whether transient, peri-irradiation Hh pathway inhibitioncan protect TACs from ionizing radiation (IR) and mitigate alopecia. Material/Methods: Female C57BL/6 mice at postnatal day 32 (early–full anagen) had dorsal pelage shaved. Cyclopamine (local intradermal Hh inhibitor) was administered, followed 6 h later by a single 5.5-Gy dorsal IR. Skin was collected at multiple post-IR time points for hematoxylin–eosin, immunohistochemistry, and dual-marker staining to assess follicle cycling, TAC apoptosis, Cyclin D1, phospho-Rb, and p53. A short-course CDK4/6-inhibitor cohort tested cell-cycle specificity. Bulge stem-cell activation was evaluated histologically. Results: IR alone produced severe anagen hair-follicle dystrophy. Brief pre-IR Hh suppression created a reversible, G1-biased pause in matrix TACs (reduced Cyclin D1 and Rb phosphorylation). Delivering IR within this window attenuated p53 induction and TAC apoptosis, preserved follicular architecture and a larger TAC pool, accelerated post-injury regeneration, and markedly reduced alopecia. Repair proceeded without bulge stem-cell activation, implicating TAC-
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