S2641
Radiobiology - Tumour radiobiology
ESTRO 2026
Digital Poster 4654 Axl tyrosine kinase as a potential target for radiosensitization in head and neck squamous cell carcinoma (HNSCC) Carla Popp 1 , Safayat Mahmoud Khan 1,2 , Lydia Koi 3,4 , Verena Bitto 1 , Wahyu Hadiwikarta 5,6 , Michael Baumann 1,6 , Ina Kurth 1,6 , María José Besso 1,2 1 Radiooncology/ Radiobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 2 Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO) and National Center for Radiation, Heidelberg, Germany. 3 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 4 OncoRay, National Center for Radiation Research in Oncology, Faculty of Medicine, Helmholtz-Zentrum Dresden - Rossendorf, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. 5 Radiooncology/ Radiobiology, German Cancer Research Center (DKFZ), Heidelberg., Germany. 6 Core Center Heidelberg, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany Purpose/Objective: Head and neck squamous cell carcinoma (HNSCC) is a clinically and molecularly heterogeneous disease with limited options for overcoming radioresistance. The receptor tyrosine kinase AXL, a member of the TAM family (Tyro3, AXL, Mer), is often overexpressed in HNSCC and implicated in tumor progression, therapeutic resistance, and epithelial–mesenchymal transition. While preclinical studies suggest that AXL inhibition may enhance radiotherapy efficacy, the precise contribution of AXL to radiotherapy responses, particularly in relation to TP53 status, remains unresolved. TP53, one of the most frequently mutated genes in HNSCC, regulates DNA damage responses and cell fate after irradiation. Prior research suggests cross-regulation between AXL and TP53. This study elucidates the relationship between AXL expression, TP53 mutation status, and radiotherapy response in HNSCC, with the goal of informing targeted radiosensitization strategies. Material/Methods: AXL expression and its relationship to TP53 status were investigated in a panel of HNSCC cell lines (SAS, FaDu, SAT, Cal 33, UT-SCC 5, UT-SCC 8, UT-SCC 14, UT- SCC 15, UM-SCC 17A, SCC 61) utilizing Western blot and quantitative PCR for protein and mRNA quantification. Immunohistochemical staining determined AXL spatial distribution. Clonogenic assays, cell viability measurements, and senescence analyses (beta-galactosidase staining) assessed functional outcomes after AXL inhibition and radiation
an acousto-holographic system before irradiation, and at 2 and 24 hours post-irradiation, on samples containing 20,000 and 50,000 cells. Measurements aimed to assess the early mechanical response of cells to ionizing radiation. Experiments with A549 p53 knockout cells and TGF- β treatment are ongoing to evaluate further the combined impact of p53 loss and TGF- β activation on mechanotransduction and matrix adaptation. Results: Preliminary findings revealed a time-dependent decrease in stiffness in A549 cells after irradiation. Softening was evident at 2 hours and became stronger at 24 hours, suggesting cytoskeletal reorganization and reduced mechanical resistance. Acousto- holographic stiffness maps confirmed lower stiffness in irradiated cells compared to controls. These results indicate that mechanical alterations may serve as early biophysical markers of radiation response and apoptosis initiation
Figure 1. Acousto-holographic stiffness maps of A549 cells before and after 6 Gy irradiation. Top: 0 Gy controls; middle: 2 h after irradiation; bottom: 24 h after irradiation. The colour scale (0–600) indicates relative intracellular stiffness. A marked stiffness reduction, particularly at 24 h, demonstrates radiation- induced softening of A549 cells. Conclusion: Following radiotherapy, lung cancer cells exhibited decreased mechanical stiffness due to cytoskeletal alterations. This softening may increase deformability and influence metastatic potential. Radiotherapy also strongly activates the TGF- β signalling pathway, which, in the absence of p53, shifts from a suppressive to a tumour-promoting phenotype. These results provide insight into why some tumours become more aggressive after radiotherapy. The findings help understand how post-radiation TGF- β activation relates to tumour invasion and circulating tumour cell development. Ongoing studies will characterise long- term adaptive responses of irradiated cancer cells within 3D matrix environments, ultimately aiming to identify strategies to prevent post-radiation metastasis. Keywords: Mechanotransduction,TGF- β signalling,Radiotherapy
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