While attempts to develop clinically effective DNA repair inhibitors have been ongoing for decades, such as O6-benzylguanine (O6-BG) for the inhibition of O6-methylguanine DNA methyltransferase (MGMT) (42), recent efforts in the identification of cancer-specific gene dependencies reveal a significant benefit in targeting proteins of the DDR, a focus of the reports highlighted herein. The gene discussed is MGMT; the disease is cancer.