The DNA damage response (DDR) pathway is a ubiquitous pathway that can be activated by kinds of DNA damage. Genomic alterations in DDR genes are associated with increased genomic instability and higher tumor mutational burden (TMB). A better understanding of DDR alterations will not only inform our knowledge of cancer development but also help to refine the classification as well as the treatment of various cancers. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients reveal distinct mutational profiles.