PhD defence G. (Grada) van de Kamp

Below is a brief summary of the dissertation: 

Radiotherapy and chemotherapy are key treatments for cancer, working by inducing DNA damage in tumor cells, ultimately leading to cell death. Despite the effectiveness of these treatments, treatment efficacy can be improved and resistant tumors remain a major challenge, underscoring the need for strategies to overcome resistance and improve efficacy. This research focused on DSBs, as they are among the most lethal forms of DNA damage, leading to cell death when left unrepaired. The study aimed to understand how cells repair DSBs caused by different types of radiation, including X-rays, proton radiation, and alpha particle radiation, as well as DNA crosslinkers like cisplatin. Specifically, the study examined three key DSB repair mechanisms: non-homologous end joining (NHEJ), homologous recombination (HR), and theta-mediated end joining (TMEJ). Key findings include that proton radiation induces DNA damage that depends more on HR for repair compared to X-ray radiation, and that TMEJ plays a crucial role in cell survival after DNA crosslinker treatment in cells deficient in NHEJ or HR. These results contribute to the development of combination therapies and personalized treatment strategies, enhancing the effectiveness of radiotherapy and DNA crosslinker therapy for cancer patients.