Targeting autophagy to enhance oncolytic virus-based cancer therapy

Introduction: Autophagy is a conserved catabolic process crucial in maintaining cellular homeostasis. On infection, oncolytic viruses (OVs) perturb the cellular autophagy machinery in infected tumor cells both in vitro and in vivo. Currently, pharmacological modulation of autophagy in OV-infected tumor cells has been shown to augment OV-mediated antitumor effects in preclinical studies. Combination of OVs with autophagy modulators can, therefore, have many potential applications in the future research on targeting autophagy and novel anticancer therapies. Areas covered: This review provides a detailed description of known interactions between OVs and autophagy and summarizes the roles of autophagy in OV replication and cell lysis. The recent literature on targeting autophagy with either the autophagy inducers, such as rapamycin, or autophagy inhibitors, such as chloroquine, to increase OV-induced cytotoxicity is reviewed to help researchers in further investigations. The major challenge for investigators is to understand the molecular mechanism underlying the interplay between OV and the autophagy machinery and its effect on oncolysis. Expert opinion: Targeting the cellular autophagy machinery could be explored as a new therapeutic strategy to enhance OV-mediated antitumor effects in the future.

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