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Dichotomies in cancer research: some suggestions for a new synthesis

Nature Clinical Practice Oncology volume 3, pages 364–373 (2006)Cite this article

Abstract

Continuing high cancer incidence and mortality raise concern about the prevailing overall approach to the control of this disease. The purpose of this article is to elaborate on fundamental dichotomies between traditional and revisionist viewpoints and then to attempt a synthesis of these contrasting perspectives. Topics considered include the importance of controlling carcinogenesis in its earliest stages; consideration of epigenetic, as well as genetic, factors in cancer; development of appropriate genetic animal models of carcinogenesis; the need for multifunctional agents to prevent and treat cancer; and the limits of reductionism. The need for development of new preventive and therapeutic measures that will maintain quality of life, not merely extend life, is stressed. Finally, the importance of context in cancer biology is emphasized, as epitomized in Walt Whitman's famous quotation that “Nothing out of its place is good and nothing in its place is bad.”

Key Points

  • Prevention of early-stage disease should be emphasized rather than directing efforts only at treating end-stage disease

  • Epigenetics is equally important as genetics, and a greater appreciation of epigenetics is pivotal to our understanding the process of carcinogenesis

  • Multifactorial animal model experiments that utilize not only transgenic mouse models, but also classical carcinogenesis models that disrupt multiple genes, are more representative models of human carcinogenesis

  • The combination of monofunctional and multifunctional agents is needed for developing both preventive and therapeutic strategies

  • A reductionist approach does not encompass the complexity of carcinogenesis or its context; instead it should be recognized that cellular networks are highly interactive systems that respond rapidly to environmental perturbation

  • Observational and hypothesis-driven research are both required to encompass a holistic approach to our understanding of cancer

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Figure 1: Target illustrating the goals of the eminent Swiss engineer, Christian Menn, in his design of a new bridge.

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Acknowledgements

I thank K Liby, L Wakefield, A Roberts, C Nathan, C Leaf, L Hutchinson, K McGaughy, and CDS for helpful comments and M Padgett for expert editorial assistance. This article is dedicated to C Everett Koop, true hero and outspoken champion of the cause of prevention of disease. Work supported by NIH grants, National Foundation for Cancer Research, members of the Dartmouth College Class of 1934, and Reata Pharmaceuticals.

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  1. MB Sporn is Professor of Pharmacology and Medicine at Dartmouth Medical School, Hanover, NH, USA

    Michael B Sporn

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Sporn, M. Dichotomies in cancer research: some suggestions for a new synthesis. Nat Rev Clin Oncol 3, 364–373 (2006). https://doi.org/10.1038/ncponc0536

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