Targeting DNA repair for precision radiotherapy: Balancing the therapeutic ratio

Genomic instability is underpinned by defects in the DNA damage response and DNA repair pathways. Subsequent clonal selection and adaption can lead to a mutator phenotype and tumor aggression. Importantly, tumor cell sensitivity to chemotherapy and radiotherapy can depend highly on the cellular capacity to repair DNA damage within and between tumor types. Annotation of functional defects in DNA damage response and DNA repair function may allow for the development of novel prognostic biomarkers. This information could also be used to predict therapeutic response, including predicting responses following inhibition of DNA repair. Herein, we highlight the increasing potential for annotating and targeting DNA repair defects in patients undergoing precision radiotherapy.