Cardiovascular dysfunction after cancer radiation therapy: search for biomarkers and study of the underlying physiological mechanisms.

The increasing effectiveness of multimodality cancer treatment, including medical imaging for diagnosis followed by surgery, chemotherapy, and radiation therapy, has significantly improved the outcome for many cancer patients. However, this also implies that long-term side effects inducted by therapy have become an important issue. External beam radiation therapy (RT) plays an important role in the management of patients with cancer. For instance, in breast cancer RT also covers part of the heart and major blood vessels. Moreover, low to mediate radiation doses associated with RT have been correlated with an increased cardiovascular morbidity and mortality. In the framework of the recently launched European Horizon2020 project MEDIRAD, we aim to explore: i) DNA methylation patterns as relevant biomarkers of radiation-induced cardiovascular damage. To this end, we will first identify DNA methylation patterns in blood samples of animal models exposed to ionizing radiation. Next, the developed biomarker panel will be cross-validated in blood samples from breast cancer RT-therapy patients (Early-Heart cohort). In parallel, we will study the effect of low-dose radiation on vascular reactivity and associated vascular stiffness in animal models. ii) microRNAs (miRNAs) and long (lncRNAs) non-coding RNAs as biomarkers for diagnosis and prognosis of cancer (e.g. after CT radiation exposure). A number of miRNA and lncRNA have been identified recently as important epigenetic regulators with critical roles in cancer invasion (such as miR-128, miR-129-2, miR-215, HOTAIR, MEG3). These epigenetic regulators affect gene expression without changing the DNA sequence. We will develop an RT-PCR assay made of up to 20 candidate miRNA and/or lncRNA identified based on data-mining of web-accessible databases. Next, blood and saliva samples from patients with brain tumours, leukaemia and healthy controls (all from the EpiCT study) will be analysed to investigate whether miRNA/lncRNAs are potential markers of radiosensitivity and may predict the development of specific malignancies. Taken together, this research project aims to identify a set of predictive biomarkers for a more accurate risk estimation for early and late radiation-induced cardiovascular and neoplastic events, as well as to provide potential targets for countermeasures. As such, we strive for a better life quality for ionizing radiation exposed people.

Keywords:CARDIOVASCULAR DISORDERS

Disciplines:Cardiac and vascular medicine

Project type:Collaboration project