PhD defence S.J. (Stefan) Roobol

Ionizing radiation (IR) can induce a wide array of different types of DNA damage and, in the context of cancer therapy, is used to eradicate tumor cells. However, cells have evolved DNA damage repair mechanisms that can counteract the DNA damaging effects, possibly leading to IR resistance. The most harmful type of DNA damage are DNA double-stranded breaks (DSBs) that are repaired in two manners, Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). More understanding how HR and NHEJ function together in DSBs repair, could improve cancer therapy based on IR or counter IR resistance.

In cancer therapy, tumors are mostly treated from outside the body, using external beam radiation therapy (EBRT). However, irradiation of tumors deep within the body can lead to toxicity. The development of radiopharmaceutical therapy (RPT) has improved treatment of cancers that are located deep in the body. In RPT, radionuclides are directed to the tumor via the bloodstream. Internal irradiation provides the possibility to use radiation with a high linear energy transfer (LET), which is not an option for external irradiation due to a low penetration depth. However, to deliver the high-LET radiation efficiently and what types of DNA damage are inflicted is not yet fully understood.

This thesis describes; (1) The cooperation of NHEJ and HR in IR protection in mice and cells; (2) the development of a novel high-LET external irradiation device; (3) the differences in DSB processing after high- and low-LET irradiation and (4) investigation of safe delivery of high-LET radionuclides using polymersomes.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall or in the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.