Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Viruses: tools for tumor target discovery, and agents for oncolytic therapies – an introduction

Oncogene volume 24, pages 7636–7639 (2005)Cite this article

Viruses, traditionally synonymous with disease, are some of the oncologist's greatest allies in providing the necessary intelligence and weaponry to wage the war on cancer. Over half a century ago, it was known that both RNA and DNA viruses could induce tumors in animals. Encoding relatively few genes, viruses are a simple genetic system with which to study the transformation of animal cells. RNA retroviruses were found to transform animal cells by ‘capturing’ and activating cellular proto-oncogenes, leading to the discovery of the first oncogene, v-src. The nucleic acid cousins of the retroviruses, DNA viruses, have also provided fundamental insights into tumorigenesis. With exquisite symmetry to its discovery in transforming retroviruses, src was also identified as a critical target of the transforming polyomavirus Middle T antigen. DNA viruses encode proteins that induce a rapid ‘tumor-like’ state in infected cells to facilitate their pathological replication. As such, DNA viral proteins and tumor cell mutations converge in subverting many of the same cellular pathways and checkpoints. Thus, many of the critical tumor targets were first identified through their interaction with DNA viral proteins, including p53 and PI3-kinase. Furthermore, our first insights into the cellular pathways that cooperate to elicit transformation were with combinations of DNA viral and cellular oncogenes. Thus, studies with viruses elucidated many of the critical tumor targets, and were our first steps down the path to rational-targeted therapies such as the bcr-abl (src kinase) inhibitor, Gleevec.

Nevertheless, in this brave new world of high throughput genomics, the utility of viruses as tools in cancer research may to some seem comparatively blunt instruments. After all, microarrays can be used to directly discover the differences between neoplastic and primary cells. However, ‘more’ is not always better. Such analyses, as often as not, leave us with a conundrum: of the myriad of differences observed, which are the key changes that maintain or drive the neoplastic phenotype? Unfortunately, the instability inherent to cancer genomes, together with their relatively short evolutionary time-span, can make it difficult to discern a priori the ‘joy-riders’ from the molecular culprits that actually drive tumorigenesis. Distinguishing between that which is coincidental and causal is paramount for the development of effective tumor therapies, which is why retroviral insertional mutagenesis screens and DNA viral proteins are still such invaluable tools. Nevertheless, enumerating critical tumor targets is of little value to a cancer patient in the absence of effective therapies that treat them. Factors that have limited the clinical successes of cancer therapies include multiple tumor cell mutations as well as the lack of cytolytic drugs. Thus, there is a great need to develop novel therapeutic modalities, rational drug combinations, and lytic agents for the treatment of cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  • Aghi M and Martuza RL . (2005). Oncogene, 24, 7802–7816.

  • Ahuja D, Sáenz-Robles MT and Pipas JM . (2005). Oncogene, 24, 7729–7745.

  • Arroyo JD and Hahn WC . (2005). Oncogene, 24, 7746–7755.

  • Barber GN . (2005). Oncogene, 24, 7710–7719.

  • Berk AJ . (2005). Oncogene, 24, 7673–7685.

  • Freeman-Cook L and DiMaio D . (2005). Oncogene, 24, 7756–7762.

  • Ko D, Hawkins L and Yu D-C. (2005). Oncogene, 24, 7763–7774.

  • Mathis JM, Stoff-Khalili MA and Curiel DT . (2005). Oncogene, 24, 7775–7791.

  • McCormick F . (2005). Oncogene, 24, 7817–7819.

  • Mohr I . (2005). Oncogene, 24, 7697–7709.

  • O'Shea CC . (2005). Oncogene, 24, 7640–7655.

  • Shmulevitz M, Marcato P and Lee PW . (2005). Oncogene, 24, 7720–7728.

  • Uren AG, Kool J, Berns A and van Lohuizen M . (2005). Oncogene, 24, 7656–7672.

  • Weitzman MD and Ornelles DA . (2005). Oncogene, 24, 7686–7696.

  • Working PK, Lin A and Borellini F . (2005). Oncogene, 24, 7792–7801.

Download references

Author information

Authors and Affiliations

  1. Cancer Research Institute, University of California San Francisco, 2340 Sutter Street, N315, San Francisco, 94115, CA, USA

    Clodagh C O'Shea

Authors
  1. Clodagh C O'Shea
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clodagh C O'Shea.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'Shea, C. Viruses: tools for tumor target discovery, and agents for oncolytic therapies – an introduction. Oncogene 24, 7636–7639 (2005). https://doi.org/10.1038/sj.onc.1209035

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209035

Keywords

This article is cited by

Search

Advanced search

Quick links