Several lines of evidence show that synthetic lethal interactions targeting DNA repair pathways may have clinical applications in cancer therapy. In a recent paper, Albarakati et al. demonstrate that BRCA1-BER deficient cells can be the target of a synthetic lethality approach by using ATM or DNA-PKcs inhibitors. (1) This publication also highlights the robustness of the SilenciX cellular models in drug discovery and particularly in synthetic lethality approaches.