DNA-damaging cancer cells to improve virotherapy

Abstract

In the current issue of MTO, an interesting work by Koch and colleagues reveals that perturbing the DNA damage response (DDR) signaling pathway enhances the cytotoxic effect of local treatment with CAN-2409, a first-generation adenoviral vector encoding the suicide gene herpes simplex virus thymidine kinase (HSV-tk), which in the presence of ganciclovir causes DNA damage, and immunogenic cell death and that is already in clinical trials in high-grade gliomas.1,2,3 The authors evaluate the efficacy of ATR/ATM inhibitors in combination with the virus in vitro and in vivo in immunocompetent mouse models to decipher its effect in tumor immune microenvironment using state-of-the-art technologies such as cytometry by time of flight (CyTOF).