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Heat shock phenocopies E1B-55K late functions and selectively sensitizes refractory tumor cells to ONYX-015 oncolytic viral therapy.

Authors
Type
Published Article
Journal
Cancer Cell International
Publisher
Springer (Biomed Central Ltd.)
Volume
8
Issue
1
Pages
61–74
Source
O'Shea Lab
License
Unknown

Abstract

ONYX-015 is an E1B-55K-deleted adenovirus that has promising clinical activity as a cancer therapy. However, many tumor cells fail to support ONYX-015 oncolytic replication. E1B-55K functions include p53 degradation, RNA export, and host protein shutoff. Here, we show that resistant tumor cell lines fail to provide the RNA export functions of E1B-55K necessary for ONYX-015 replication; viral 100K mRNA export is necessary for host protein shutoff. However, heat shock rescues late viral RNA export and renders refractory tumor cells permissive to ONYX-015. These data indicate that heat shock and late adenoviral RNAs may converge upon a common mechanism for their export. Moreover, these data suggest that the concomitant induction of a heat shock response could significantly improve ONYX-015 cancer therapy.

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