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The aging of the 2000 and 2011 Hallmarks of Cancer reviews: A critique

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ABSTRACT

Two review articles published in 2000 and 2011 by Hanahan and Weinberg have dominated the discourse about carcinogenesis among researchers in the recent past. The basic tenets of their arguments favour considering cancer as a cell-based, genetic disease whereby DNA mutations cause uncontrolled cell proliferation. Their explanation of cancer phenotypes is based on the premises adopted by the somatic mutation theory (SMT) and its cell-centered variants. From their perspective, eight broad features have been identified as so-called ‘Hallmarks of Cancer’. Here, we criticize the value of these features based on the numerous intrinsic inconsistencies in the data and in the rationale behind SMT. An alternative interpretation of the same data plus data mostly ignored by Hanahan and Weinberg is proposed, based instead on evolutionarily relevant premises. From such a perspective, cancer is viewed as a tissue-based disease. This alternative, called the tissue organization field theory, incorporates the premise that proliferation and motility are the default state of all cells, and that carcinogenesis is due to alterations on the reciprocal interactions among cells and between cells and their extracellular matrix. In this view, cancer is development gone awry.

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Notes

  1. To avoid repetitions of the names of Hanahan and Weinberg and ‘The hallmarks of cancer’ articles from 2000 and 2011, we will use the acronyms H&W, and Hallmarks I and Hallmarks II, respectively.

  2. In Longo et al. (2012), we criticize the use of metaphors in biology.

  3. The success of molecular biology techniques when sequencing the human and other genomes exposed the unsustainability of reductionistic, of linear thinking, genetic determinism and additional failed ideologies. These issues are analysed in the book Genetic explanations: Sense and nonsense (eds) S Krimsky and J Gruber 2013 (Cambridge, MA: Harvard University Press).

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Acknowledgements

We thank Cheryl Schaeberle for her help in the editing and the preparation of this manuscript. The work was supported by the Avon Foundation grant no. 02-2011-095 as well as by the National Institute of Environmental Health Sciences, Award Number R01ES08314. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences or the National Institutes of Health.

Note added in proof

In a recent article, researchers committed to the SMT conclude that most mutations in genes proposed to be ‘drivers’ of carcinogenesis, as originally described by The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium, represent instead false positives. This conclusion gleaned from sophisticated data-mining computer models suggests that those alleged driver genes remain elusive and their nature is subject to the premises of the model used to find them (Lawrence MS et al. 2013 Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature. DOI: 10.1038/nature12213).

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  1. Tufts University School of Medicine, Program on Cellular, Developmental and Molecular Biology, Boston, MA, 02111, USA

    Carlos Sonnenschein & Ana M Soto

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  1. Carlos Sonnenschein
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  2. Ana M Soto
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Correspondence to Ana M Soto.

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Corresponding editor: INDRANEEL MITTRA

MS received 28 January 2013; accepted 08 April 2013

Corresponding editor: Indraneel Mittra

[Sonnenschein C and Soto AM 2013 The aging of the 2000 and 2011 Hallmarks of Cancer reviews: A critique. J. Biosci. 38 1–13] DOI 10.1007/s12038-013-9335-6

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Sonnenschein, C., Soto, A.M. The aging of the 2000 and 2011 Hallmarks of Cancer reviews: A critique. J Biosci 38, 651–663 (2013). https://doi.org/10.1007/s12038-013-9335-6

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