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  • Review Article
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Review Article

Replication-selective oncolytic adenoviruses: virotherapy aimed at genetic targets in cancer

Oncogene volume 19, pages 6660–6669 (2000)Cite this article

The clinical utility of any cancer treatment is defined by both its antitumoral potency and its therapeutic index between cancerous and normal cells. Chemotherapy for metastatic solid tumors generally fails due to an insufficient therapeutic index and/or insufficient antitumoral potency. Although standard agents target a variety of different structures within cancer cells, almost all of them are thought to kill cancer cells through the induction of apoptosis. As a result, apoptosis-resistant clones develop following standard therapies, even if numerous high-dose chemotherapeutic agents are used in combination. Novel therapeutic approaches must therefore have not only greater potency and greater selectivity than currently available treatments, they should also have novel mechanisms of action that will not be subject to cross-resistance with existing approaches (i.e. efficacy should not be exclusively dependent on apoptosis induction in cancer cells).

Revolutionary advances in molecular biology and genetics have led to a fundamental understanding of both (1) the replication and pathogenicity of viruses and (2) carcinogenesis. These advances have allowed novel agents to be engineered to enhance their safety and/or their antitumoral potency. Over the past decade, genetically-engineered viruses in development have included adenoviruses, herpesviruses and vaccinia. Viruses with inherent tumor-selectivity have been characterized and include reovirus, autonomous parvoviruses, Newcastle disease virus, measles virus strains and vesicular stomatitis virus (Kirn, 2000a). Each of these agents has shown tumor selectivity in vitro and/or in vivo, with many of these agents following intratumoral, intraperitoneal and/or intravenous routes of administration.

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Acknowledgements

The following individuals have been instrumental in making this manuscript possible: John Nemunaitis, Stan Kaye, Tony Reid, Fadlo Khuri, James Abruzzesse, Eva Galanis, Joseph Rubin, Antonio Grillo-Lopez, Carla Heise, Larry Romel, Chris Maack, Sherry Toney, Nick LeMoine, Britta Randlev, Patrick Trown, Fran Kahane, Frank McCormick and Margaret Uprichard.

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  1. Imperial Cancer Research Fund, Program for Viral and Genetic Therapy of Cancer, Imperial College School of Medicine, Hammersmith Hospital, DuCane Road, London, W12 0NN, UK

    David Kirn

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Kirn, D. Replication-selective oncolytic adenoviruses: virotherapy aimed at genetic targets in cancer. Oncogene 19, 6660–6669 (2000). https://doi.org/10.1038/sj.onc.1204094

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