These findings suggest that targeting a backup repair pathway to which cancer cells are addicted could be exploited to selectively kill tumor cells while sparing normal cells, making therefore Alt-NHEJ a promising target for the treatment of DNA damage response (DDR)-deficient cancer cells [64].There are three main strategies to target Alt-NHEJ repair: (1) inhibiting the first step by PARPis, (2) preventing DNA synthesis at gaps targeting PolQ, and (3) blocking the final step of DNA end joining by DNA ligases inhibitors. This evidence concerns the gene POLQ and cancer.