Cancers, Vol. 12, Pages 798: External Beam Radiation Therapy and Enadenotucirev: Inhibition of the DDR and Mechanisms of Radiation-Mediated Virus Increase

Cancers, Vol. 12, Pages 798: External Beam Radiation Therapy and Enadenotucirev: Inhibition of the DDR and Mechanisms of Radiation-Mediated Virus Increase Cancers doi: 10.3390/cancers12040798 Authors: Tzveta D. Pokrovska Egon J. Jacobus Rathi Puliyadi Remko Prevo Sally Frost Arthur Dyer Richard Baugh Gonzalo Rodriguez-Berriguete Kerry Fisher Giovanna Granata Katharine Herbert William K. Taverner Brian R. Champion Geoff S. Higgins Len W. Seymour Janet Lei-Rossmann Ionising radiation causes cell death through the induction of DNA damage, particularly double-stranded DNA (dsDNA) breaks. Evidence suggests that adenoviruses inhibit proteins involved in the DNA damage response (DDR) to prevent recognition of double-stranded viral DNA genomes as cellular dsDNA breaks. We hypothesise that combining adenovirus treatment with radiotherapy has the potential for enhancing tumour-specific cytotoxicity through inhibition of the DDR and augmentation of virus production. We show that EnAd, an Ad3/Ad11p chimeric oncolytic adenovirus currently being trialled in colorectal and other cancers, targets the DDR pathway at a number of junctures. Infection is associated with a decrease in irradiation-induced 53BP1 and Rad51 foci formation, and in total DNA ligase IV levels. We also demonstrate a radiation-associated increase in EnAd production in vitro and in a pilot in vivo experiment. Given the current limitations of in vitro techniques in assessing for synergy...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research