Changes in prostate-specific membrane antigen expression following ionizing irradiation – Implications for clinical practice
Final Report Abstract
Prostate-specific membrane antigen (PSMA) represents an attractive target structure for diagnostic and therapeutic approaches in patients with all stages of prostate cancer (PCa). However, regulatory mechanisms of PSMA expression still remain unclear. The project addresses a detailed analysis on the impact of ionizing radiation on PSMA expression levels in PCa cells in a dose and time dependent manner. Furthermore, the potential of PSMA to serve radio protective for PCa cells was evaluated and the effect of PSMA inhibitors for increased radio-sensitivity of PCa cells examined. Finally, translating these study outcomes to clinical application, a combination with therapeutical approaches was performed. As increased PSMA levels through ionizing irradiation may improve the efficiency of PSMA- targeted therapeutic approaches, a sequential treatment protocol with ionizing irradiation followed by PSMA-targeted endo-radiotherapy (PSMA-RLT) was investigated. Hence, this project comprises a scientific working program incorporating cell culture studies, primary PCa tissue and preclinical therapeutical studies in a highly multidisciplinary environment. The project outcome provides an insight into the influence of ionizing radiation on PSMA expression in PCa and the resulting consequences for synergistic therapeutical approaches in the management of PCa patients.
Publications
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Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer—Combination Strategies. Current Oncology Reports, 25(11), 1363-1374.
Arbuznikova, Daria; Eder, Matthias; Grosu, Anca-Ligia; Meyer, Philipp T.; Gratzke, Christian; Zamboglou, Constantinos & Eder, Ann-Christin
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Exploring the role of combined external beam radiotherapy and targeted radioligand therapy with [177Lu]Lu-PSMA-617 for prostate cancer - from bench to bedside. Theranostics, 14(6), 2560-2572.
Arbuznikova, Daria; Klotsotyra, Aikaterini; Uhlmann, Lisa; Domogalla, Lisa-Charlotte; Steinacker, Nils; Mix, Michael; Niedermann, Gabriele; Spohn, Simon K.B.; Freitag, Martin T.; Grosu, Anca L.; Meyer, Philipp T.; Gratzke, Christian; Eder, Matthias; Zamboglou, Constantinos & Eder, Ann-Christin
