Cancer is considered as one of the principal cause of death worldwide1. However, these past years, new technologies and knowledge on cancer cells arose which led to the development of more specific treatments, better adapted to each tumor, resulting in better outcomes for the patients. This approach often relies on the discovery of new synthetic lethal interactions between drug compounds and tumor-specific gene expression. ATR (ataxia telangiectasia and Rad3-related protein) is a kinase involved in many pathways of the DNA damage response and was shown to be overactivated in many different cancers. Inhibitors of this protein have been developed recently and are now used in chemotherapies to treat advanced tumors. In this report, we found that DNA damage caused by the ATR inhibitor BAY1895344 in Hela and U2OS cancerous cell lines could be increased when combined with inhibition of SMARCA4, RAD52, FBXW7, MACROD1 or PKMYT1. Understanding these synergies could further help to improve the efficiency of treatments involving ATR inhibitors.