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Serbian Association for Cancer Research SDIRSACR

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Investigation of individual radiosensitivity of prostate cancer patients under radiation treatment

Ivana Z. Matić , Tatjana Stanojković , Nina Petrović , Marina Nikitović , Marlon Veldwijk , Christopher Talbot ,
2,1
5
4
1
1
1,3
Siegfried Knasmüller , Maja Čemažar 7
6
1Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
2“VINČA“ Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
3Faculty of Medicine, University of Belgrade, Belgrade, Serbia
4Cellular and Molecular Radiation Oncology Lab, Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical
Faculty Mannheim, Heidelberg University, Germany
5Leicester Cancer Research Centre, College of Life Sciences, University of Leicester, United Kingdom
6Center for Cancer Research, Medical University of Vienna, Vienna, Austria
7Institute of Oncology Ljubljana, Ljubljana, Slovenia

Keywords: Apoptosis, DNA damage, MicroRNome, Transcriptome, Radiotherapy, Radiation toxicity

Radiotherapy plays a central role in the treatment of patients with prostate cancer. One of the main challenges in
modern radiation oncology is to develop efficient predictive models for the estimation of the radiation toxicity risk
to tailor radiation treatment to the ndividual patient, improve the therapeutic success, and minimize severe adverse
effects in cancer survivors. Numerous treatment-related, patient-specific, clinical, and biological factors, including
genetic and epigenetic factors, as well as mediators of inflammation and immune response, may affect the possible
risk of developing acute and late genitourinary and gastrointestinal radiation toxicity in prostate cancer patients
undergoing radiotherapy. The multifactorial biological background of each cancer patient is responsible for individual
differences in radiation-induced normal tissue toxicity. The investigation of the sensitivity of patient-derived peripheral
blood mononuclear cells (PBMC) to ionizing radiation using different cell-based functional assays in combination
with molecular mechanisms underlying this signature and specific acute and late radiation toxicity adverse events
in prostate cancer patients using genomic, transcriptomic, epigenomic, and proteomic profiling is essential for
identification of novel biomarkers and models for individual radiosensitivity assessment. The radiobiology research
conducted within the Horizon Europe Twinning project RadExIORSBoost at the Institute for Oncology and Radiology of
Serbia (coordinator) in collaboration with top-class leading European research institutions: Medical Faculty Mannheim
(Heidelberg University), Medical University of Vienna, University of Leicester, and Institute of Oncology Ljubljana,
aims to examine the multiple biological factors underlying individual normal tissue radiosensitivity in prostate cancer
patients treated with radiotherapy. The systems biology approach is employed to explore the functional and molecular
predictors of radiation toxicity using radiation-induced apoptosis rates of T lymphocytes, single cell gel electrophoresis
and gamma-H2AX assays to measure radiation-induced DNA strand breaks and repair kinetics in PBMCs, in addition
to transcriptome and miRNome profiling of PBMCs. Development and clinical validation of machine learning models
for predicting individual radiosensitivity by combining individual, clinical, and biological factors are essential for a
personalized radiotherapy approach.

Acknowledgments and funding: This Project is funded by the European Union, under Horizon Europe programme
Grant agreement number 101158832. Views and opinions expressed are however those of the author(s) only and
do not necessarily reflect those of the European Union or European Research Executive Agency (REA). Neither the
European Union nor the granting authority can be held responsible for them.

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