title: A high-throughput pharmacoviral approach identifies novel oncolytic virus sensitizers.
abstract: Oncolytic viruses (OVs) are promising anticancer agents but like other cancer monotherapies, the genetic heterogeneity of human malignancies can lead to treatment resistance. We used a virus/cell-based assay to screen diverse chemical libraries to identify small molecules that could act in synergy with OVs to destroy tumor cells that resist viral infection. Several molecules were identified that aid in viral oncolysis, enhancing virus replication and spread as much as 1,000-fold in tumor cells. One of these molecules we named virus-sensitizers 1 (VSe1), was found to target tumor innate immune response and could enhance OV efficacy in animal tumor models and within primary human tumor explants while remaining benign to normal tissues. We believe this is the first example of a virus/cell-based "pharmacoviral" screen aimed to identify small molecules that modulate cellular response to virus infection and enhance oncolytic virotherapy.
authors.affiliation: Ottawa Hospital Research Institute, Center for Cancer Therapeutics, Ottawa, Ontario, Canada.
authors.forename: Jean-Simon
authors.initials: JS
authors.lastname: Diallo
authors.forename: Fabrice
authors.initials: F
authors.lastname: Le Boeuf
authors.forename: Frances
authors.initials: F
authors.lastname: Lai
authors.forename: Julie
authors.initials: J
authors.lastname: Cox
authors.forename: Markus
authors.initials: M
authors.lastname: Vaha-Koskela
authors.forename: Hesham
authors.initials: H
authors.lastname: Abdelbary
authors.forename: Heather
authors.initials: H
authors.lastname: MacTavish
authors.forename: Katherine
authors.initials: K
authors.lastname: Waite
authors.forename: Theresa
authors.initials: T
authors.lastname: Falls
authors.forename: Jenny
authors.initials: J
authors.lastname: Wang
authors.forename: Ryan
authors.initials: R
authors.lastname: Brown
authors.forename: Jan E
authors.initials: JE
authors.lastname: Blanchard
authors.forename: Eric D
authors.initials: ED
authors.lastname: Brown
authors.forename: David H
authors.initials: DH
authors.lastname: Kirn
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
authors.forename: Harry
authors.initials: H
authors.lastname: Atkins
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lichty
authors.forename: John C
authors.initials: JC
authors.lastname: Bell
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy; D050130:Oncolytic Virotherapy
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