ESTRO 2025 - Abstract Book

S3981

Radiobiology - Tumour radiobiology

ESTRO 2025

References: Gorodetska I, et al. Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism. bioRxiv 2024.07.16.603771; doi: https://doi.org/10.1101/2024.07.16.603771 Gorodetska I, et al. ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR dependent transcription. Theranostics. 2024;14(2):714-737. Püschel J, et al. The Multifaceted Role of Aldehyde Dehydrogenases in Prostate Cancer Stem Cells. Cancers (Basel). 2021;13(18):4703. Peitzsch C, et al. Metabolic regulation of prostate cancer heterogeneity and plasticity. Semin Cancer Biol. 2022;82:94-119.

1681

Poster Discussion Patient-Derived Organoids of anal cancer as a translational tumor model

Elisa Thomas 1,2,3 , Lena S Heiser 2,4 , Sebastian Merker 3 , Daniel E Stange 3,5 , Claudia Ball 6,7,4 , Ivona Mateska 3 , Antje Dietrich 2,4 , Soňa Michlíková 2,8 , Thomas Groß 3,4,9 , Carina Wenzel 3,10 , Annett Linge 1,2,4 , Mechthild Krause 1,2,3 1 Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany. 2 OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden— Rossendorf, Dresden, Germany. 3 National Center for Tumor Diseases Dresden (NCT/UCC), a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany. 4 German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany. 5 Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany. 6 Department for Translational Medical Oncology, National Center for Tumor Diseases Dresden (NCT/UCC), a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany. 7 Translational Medical Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany. 8 Helmholtz-Zentrum, Dresden—Rossendorf, Dresden, Germany. 9 Core Unit for Molecular Tumor Diagnostics (CMTD), Technical University Dresden, Dresden, Germany. 10 Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany Purpose/Objective: Radiochemotherapy of anal squamous cell carcinoma (ASCC) has been the standard treatment over the last decades, despite the 5-year overall survival rate of the patients is around 60% [1]. To date, there are only a few in vitro cell culture models available for preclinical research in this rare tumor entity. Therefore, the aim was to establish patient-derived organoid (PDOs) cultures of ASCC as translational models in follow-up studies. Material/Methods: To our knowledge, no published protocols exist for creating ASCC tumor organoids; therefore, we adapted methods from Driehuis et al. [2]. We cultivated single cells and cell clusters from fresh tumor tissue in Matrigel to create 3D tumor organoids, which were then characterized histologically, molecularly and transplanted into a mouse model [3]. We performed H&E and immunohistochemical (KI67, p53, p16) staining. DNA sequencing was done using the NGS assay TruSight Oncology 500 (Illumina). We conducted high-throughput functional screening with a PrestoBlue viability assay, testing simultaneously 22 drugs with or without 4 Gy irradiation. Potential radiosensitizers were investigated further. Results: We established patient-derived organoids (PDOs) from primary anal carcinoma (n=2), recurrences (n=2), and metastases (n=1), achieving a successful long-term cultivation rate of 50% (5 out of 10 samples).