Classical ‘DNA damaging’ chemotherapy drugs can provoke mutations in surviving cells, potentially promoting therapy-related second cancers.44 Exposure to chemotherapy drugs can stimulate intrinsic apoptotic pathways that, like TRAIL signaling, involve the activation of caspases and CAD.45 We therefore tested the hypothesis that a proportion of chemotherapy-induced mutations might also be because of the mis-repair of CAD-mediated double-strand DNA breaks. The gene discussed is TNFSF10; the disease is cancer.