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Viruses – seeking and destroying the tumor program

Oncogene volume 24, pages 7640–7655 (2005)Cite this article

Abstract

DNA viruses have enormous utility in cancer research, both as tools for tumor target discovery as well as agents for lytic cancer therapies. This is because there is a profound functional overlap between the DNA viral and tumor cell programs. DNA viruses encode proteins that elicit growth deregulation in infected cells similar to that engendered by mutations in tumor cells. Evolution has refined viral proteins to target the critical cellular hubs that regulate growth. Thus, viral proteins are discriminating biochemical probes that can be used to identify and characterize novel tumor targets. Moreover, the overlap between the DNA viral and tumor programs can also be exploited for the development of lytic cancer therapies. Discovering whether tumor cells selectively complement the replication of viral mutants can reveal novel oncolytic viral therapies, as well as unexpected tumor properties. For example, altered RNA export was recently uncovered as a novel tumor cell property that underlies ONYX-015 replication, a promising oncolytic adenoviral therapy. A perspective is provided on how adenovirus could be systematically exploited to map the requisite role, or indeed the redundancy, of cellular pathways that act in an integrated program to elicit pathological replication. This knowledge has important applications for the rational design of the next generation of oncolytic viruses, as well as the discovery of efficacious combination cancer therapies.

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Acknowledgements

I would like to thank Conrado Soria for helping illustrate Figures 1 and 2. In addition, I would like to thank David Dankort, Abi Miller, David Stokoe, Frank McCormick and Mike Fried for their useful suggestions and critical reading of this manuscript. This work was supported by bio-02-10242.

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    Clodagh C O'Shea

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O'Shea, C. Viruses – seeking and destroying the tumor program. Oncogene 24, 7640–7655 (2005). https://doi.org/10.1038/sj.onc.1209047

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