DNA double-strand break repair in cancer: A path to achieving precision medicine.

The assessment of DNA damage can be a significant diagnostic for precision medicine. DNA double strand break (DSBs) pathways in cancer are the primary targets in a majority of anticancer therapies, yet the molecular vulnerabilities that underlie each tumor can vary widely making the application of precision medicine challenging. Identifying and understanding these interindividual vulnerabilities enables the design of targeted DSB inhibitors along with evolving precision medicine approaches to selectively kill cancer cells with minimal side effects. A major challenge however, is defining exactly how to target unique differences in DSB repair pathway mechanisms. This review comprises a brief overview of the DSB repair mechanisms in cancer and includes results obtained with revolutionary advances such as CRISPR/Cas9 and machine learning/artificial intelligence, which are rapidly advancing not only our understanding of determinants of DSB repair choice, but also how it can be used to advance precision medicine. Scientific innovation in the methods used to diagnose and treat cancer is converging with advances in basic science and translational research. This revolution will continue to be a critical driver of precision medicine that will enable precise targeting of unique individual mechanisms. This review aims to lay the foundation for achieving this goal.