title: The emergence of combinatorial strategies in the development of RNA oncolytic virus therapies.
abstract: Oncolytic viruses (OVs) represent an exciting new biological approach to cancer therapy. In particular, RNA viruses have emerged as potent agents for oncolytic virotherapy because of their capacity to specifically target and destroy tumour cells while sparing normal cells and tissues. Several barriers remain in the development of OV therapy, including poor penetration into the tumour mass, inefficient virus replication in primary cancers, and tumour-specific resistance to OV-mediated killing. The combination of OVs with cytotoxic agents, such as small molecule inhibitors of signalling or immunomodulators, as well as stealth delivery of therapeutic viruses have shown promise as novel experimental strategies to overcome resistance to viral oncolysis. These agents complement OV therapy by unblocking host pathways, delivering viruses with greater efficiency and/or increasing virus proliferation at the tumour site. In this review, we summarize recent development of these concepts, the potential obstacles, and future prospects for the clinical utilization of RNA OVs in cancer therapy.
authors.affiliation: Terry Fox Molecular Oncology Group, Lady Davis Institute - Jewish General Hospital, Montreal, Quebec, Canada H3T1E2.
authors.forename: Thi Lien-Anh
authors.initials: TL
authors.lastname: Nguyen
authors.forename: Vanessa Fonseca
authors.initials: VF
authors.lastname: Tumilasci
authors.forename: Diane
authors.initials: D
authors.lastname: Singhroy
authors.forename: Meztli
authors.initials: M
authors.lastname: Arguello
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D012328:RNA Viruses / Q000254:growth & development*
chemical_list: D000970:Antineoplastic Agents