P9 - Preclinical models of prostate cancer research
Sabrina Köcher & Wael Mansour
Laboratory for Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf
To date, many questions in the field of PCa translational research cannot be adequately answered due to the lack of an appropriate preclinical model that represents PCa in vivo.
Ex-vivo Assay:
For that reason, we successfully established an ex-vivo assay using tumor slice cultures to follow DSB repair as well as to test new treatment strategies. This assay was already used to identify DSB repair defects in human xenograft tumors as well as in numerous human PCa samples. Using this assay, we are trying to answer several questions related to DNA repair in PCa and to rationalize the use of specific DNA repair inhibitors or second generation antiandrogens to potentiate the effect of radiotherapy.
Patient-derived organoids:
We also established patient-derived PCa organoids (PCa PDO) to be used as pre-clinical models in PCa translational research. We established isolation, cultivation and growth conditions which enable optimum growth of PCa PDO. We could show that our established PDOs reflect – to a large extent – the properties of original tumours. Currently, we are performing further optimization and fine establishment of PDO cultures to use as pre-clinical models for translational tumour research.
Grants: BMBF, FFM, Monika Kutzner Stiftung, German Cancer Aid
Contact: w.mansour@uke.de
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Selected publications on topic
Preclinical patient-derived modelling of castration-resistant prostate cancer facilitates individualized assessment of homologous recombination repair deficient disease. Elsesy ME, Oh-Hohenhorst SJ, Oing C, Eckhardt A, Burdak-Rothkamm S, Alawi M, Müller C, Schüller U, Maurer T, von Amsberg G, Petersen C, Rothkamm K, Mansour WY.Mol Oncol. 2023 Jan 24. doi: 10.1002/1878-0261.13382. Online ahead of print.PMID: 36694344
Establishment of a Transformation Coupled in vitro End Joining Assay to Estimate Radiosensitivity in Tumor Cells. Degenhardt S, Dreffke K, Schötz U, Petersen C, Engenhart-Cabillic R, Rothkamm K, Dahm-Daphi J, Dikomey E, Mansour WY.Front Oncol. 2020 Aug 20;10:1480. doi: 10.3389/fonc.2020.01480. eCollection 2020.PMID: 32974177
A functional ex vivo assay to detect PARP1-EJ repair and radiosensitization by PARP-inhibitor in prostate cancer. Köcher S, Beyer B, Lange T, Nordquist L, Volquardsen J, Burdak-Rothkamm S, Schlomm T, Petersen C, Rothkamm K, Mansour WY.Int J Cancer. 2019 Apr 1;144(7):1685-1696. doi: 10.1002/ijc.32018. Epub 2019 Jan 5.PMID: 30478958