UBT-Rad

Unraveling brain tumor formation after low dose irradiation exposure

Project objectives and goals

The incidence of pediatric brain tumors follows a constant increase. Among the risk factors in children and adolescents, high dose ionizing radiation (HDIR) are the strongest documented. There are a few established risk factors for CNS tumors in children and adolescents, including inherited disorders and ionizing radiation. The EPI-CT study suggest a linear increase in the relative rate of cancer with radiation dose to the brain from CT examinations. However, many factors, including age, gender, lifestyle, environment, and genetic backgrounds may influence the radiosusceptibility. Here, we hypothesize that low dose irradiation (LDIR), received in children could be a driven factor of the neoplastic acquisition and promoted by genetic mutations. We also aim to explore other mechanisms that may modulate brain tumor formation on focusing on three main topics: brain microenvironment, immune reaction, and redox status. Last, we aim to identity and inhibit factors that would disable tumor progression. The present study has been designed around six WPs. Firstly, we will work in vitro on the initiation of tumor formation from neural stem cells and astrocytes that will be initiated following genetic modifications (NBS1/TP53/PTEN). Once prepared, these cells will be irradiated and neoplastic transformation will be measured (WP2). Therefore, WP2 will correspond to the identification of intrinsic mechanisms underlying LDIR-induced brain carcinogenesis. WP3 will correspond to the identification of the role of the brain microenvironment (microglia, astrocytes, endothelial cells) using in vitro (cocultures and supernatant transfer) and ex vivo (organotypic slices) approaches. WP4 will correspond to in vivo assessment the effects of LDIR exposure on brain tumor incidence, survival animal and the identification of early biomarkers (relative to HDIR) as a function of age and sex and in or out-of-field irradiation (whole-brain, hemibrain or brainless whole-body). WP5 will consist of teaching and education on effects of LDIR-induced carcinogenesis and WP6 will correspond to dissemination. WP1 will be dedicated to project coordination. The UBT-Rad project is therefore design to comprehensively understand the brain tissue reaction occurring after low dose irradiation exposure and to identify factors that could in turn be inhibited to disable brain tumor formation.

 

Project coordinator

Samuel Valable, CNRS - Imaging and Therapeutic Strategies for Cancers and Brain Tissue – ISTCT, France

Deliverables

D9.130

UBT-Rad – Data Management Plan

DMP - Data management plan