Recently, Zhou et al. identified antibiotic novobiocin (NVB) as a specific potent inhibitor of human Pol θ (Figure 13) which inhibited alt-NHEJ repair and selectively killed HDR-deficient (both BRCA1- and BRCA2-deficient) cells over wild-type cells and significantly enhanced the cytotoxic effect of PARPi in HDR-deficient tumor cells in cellular as well as in xenograft and PDX mouse models (217). Here, BRCA2 is linked to neoplasm.