Radiobiology of radionuclide therapy: using molecular insights to improve treatment outcome for cancer patients.

Patients with metastasized cancers can be treated with molecular radionuclide therapies (MRT) during which radiolabeled compounds are targeted to the cancer lesions. Once bound to the tumor cells, the radionuclides will induce DNA damage leading to cancer cell death during radioactive decay. Currently, more cancer patients are being treated with MRTs than ever before. However, it is clear that some patients are being over-treated (toxicity) or under-treated (no tumor regression). This indicates the clinical need for therapy improvement. The focus of our work is on the understanding of the radiobiology, i.e. of the biological effects of ionizing radiation of MRTs, with a specific focus on DNA damage response mechanisms. By using this knowledge, we can significantly contribute to increasing the effectiveness of MRTs by providing evidence in favor of one treatment method or regimen over another. In order to answer our research questions, we are using a variety of models and tools. From 2D cultured cells and ex vivo cultured human tumor slices to xenografted mice. This broad range of models allows us to study different aspects of MRTs. We use several cellular assays, immunohistochemistry of human tumor tissue or mouse organs, confocal live-cell microscopy and small animal imaging (SPECT, MRI, optical).
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Julie Nonnekens received her MSc in Biotechnology at Wageningen University, The Netherlands in 2009. She obtained her PhD in cancer biology with the focus on DNA repair mechanisms at the University of Toulouse, France in 2013. Following, she was a postdoc at the Hubrecht Institute in Utrecht, The Netherlands working on ribosome biogenesis in cancer and longevity. In 2014 Julie joined the Erasmus MC in Rotterdam, The Netherlands and is now an assistant professor and group leader with a joint appointment at the Departments of Radiology & Nuclear Medicine and Molecular Genetics. She has started a new research line that bridges the interests of both departments in which she is using her experience in the field of DNA damage repair mechanisms to study the radiobiology of targeted radionuclide anticancer treatment in order to ultimately optimize treatment regimens. Julie has received several (young investigator) awards and is principal investigator on various research grants. She is secretary of the Netherlands Society of Radiobiology and co-founder of the European working group on Radiobiology of Molecular Radionuclide Therapy.

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