| Literature DB >> 25817275 |
Rozanne Arulanandam1, Cory Batenchuk1, Oliver Varette1, Chadi Zakaria2, Vanessa Garcia1, Nicole E Forbes1, Colin Davis1, Ramya Krishnan1, Raunak Karmacharya1, Julie Cox1, Anisha Sinha1, Andrew Babawy1, Katherine Waite1, Erica Weinstein1, Theresa Falls1, Andrew Chen1, Jeff Hamill1, Naomi De Silva1, David P Conrad1, Harold Atkins1, Kenneth Garson1, Carolina Ilkow1, Mads Kærn3, Barbara Vanderhyden1, Nahum Sonenberg2, Tommy Alain4, Fabrice Le Boeuf1, John C Bell1, Jean-Simon Diallo1.
Abstract
In this study, we show that several microtubule-destabilizing agents used for decades for treatment of cancer and other diseases also sensitize cancer cells to oncolytic rhabdoviruses and improve therapeutic outcomes in resistant murine cancer models. Drug-induced microtubule destabilization leads to superior viral spread in cancer cells by disrupting type I IFN mRNA translation, leading to decreased IFN protein expression and secretion. Furthermore, microtubule-destabilizing agents specifically promote cancer cell death following stimulation by a subset of infection-induced cytokines, thereby increasing viral bystander effects. This study reveals a previously unappreciated role for microtubule structures in the regulation of the innate cellular antiviral response and demonstrates that unexpected combinations of approved chemotherapeutics and biological agents can lead to improved therapeutic outcomes.Entities:
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Year: 2015 PMID： 25817275 DOI： 10.1038/ncomms7410
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919