DNA double strand break repair mechanisms in response to proton radiotherapy: Implications for cancer treatment

Double strand breaks (DSBs) are highly toxic lesions that pose a significant threat to cells. To mitigate the detrimental effects of DSBs, cells have evolved multiple DSB repair pathways, including non-homologous end joining, homologous recombination, and theta-mediated end joining. Exploiting or inducing deficiencies in these repair mechanisms within tumors sensitizes them to various cancer treatments, such as ionizing radiation and interstrand crosslink inducing agents. However, tumors can develop resistance by utilizing alternative repair pathways. Thus, understanding the dynamics of DSB repair mechanisms after cancer therapies is crucial for enhancing treatment efficacy and overcoming resistance. This study systematically examined DSB repair mechanisms across different radiation modalities, X-rays, protons and alpha particles, as well as DNA crosslinking agents, highlighting opportunities for optimizing therapies through combination treatments and personalized medicine.