The selective permissiveness of cancer cells to reovirus replication and lysis is dependent on a number of factors, including: (1) defective double-stranded RNA activated protein kinase (PKR) signaling; (2) RAS activation and/or mutations in upstream and downstream RAS-effector proteins that downregulate the interferon (IFN)-induced antiviral response; (3) mutations in key tumor suppressor genes and oncogenes (e.g., p53 and ataxia telangiectasia mutated (ATM)); and (4) cellular stress resulting from chemotherapy and radiation therapy [10,11,12,13,14,15]. This evidence concerns the gene ATM and cancer.