Targeting the DNA damage response (DDR) of cancer cells with natural compounds derived from

DNA damage is a driver of cancer formation, leading to the impairment of repair mechanisms in cancer cells and rendering them susceptible to DNA-damaging therapeutic approaches. The concept of "synthetic lethality" in cancer clinics has emerged, particularly with the use of PARP inhibitors and the identification of DNA damage response (DDR) mutation biomarkers, emphasizing the significance of targeting DDR in cancer therapy. Novel approaches aimed at genome maintenance machinery are under development to further enhance the efficacy of cancer treatments. Natural compounds from traditional medicine, renowned for their anti-aging and anticarcinogenic properties, have garnered attention. Ginseng-derived compounds, in particular, exhibit anti-carcinogenic effects by suppressing reactive oxygen species (ROS) and protecting cells from DNA damage-induced carcinogenesis. However, the anticancer therapeutic effect of ginseng compounds has also been demonstrated by inducing DNA damage and blocking DDR. This review concentrates on the biphasic effects of ginseng compounds on DNA mutations-both inhibiting mutation accumulation and impairing DNA repair. Additionally, it explores other natural compounds targeting DDR directly, providing potential insights into enhancing cancer therapy efficacy.