DNA repair, genome stability and cancer: a historical perspective

Research into the DNA damage response (DDR) was recently honoured by the Nobel Prize in Chemistry and the Lasker Award. In this Timeline article, the authors provide a historical perspective on our understanding of the role of the DDR in cancer. The multistep process of cancer progresses over many years. The prevention of mutations by DNA repair pathways led to an early appreciation of a role for repair in cancer avoidance. However, the broader role of the DNA damage response (DDR) emerged more slowly. In this Timeline article, we reflect on how our understanding of the steps leading to cancer developed, focusing on the role of the DDR. We also consider how our current knowledge can be exploited for cancer therapy.