Abstract

We propose that carcinogenesis requires tumour populations to surmount six distinct microenvironmental proliferation barriers that arise in the adaptive landscapes of normal and premalignant populations growing from epithelial surfaces. Somatic evolution of invasive cancer can then be viewed as a sequence of phenotypical adaptations to these barriers. The genotypical and phenotypical heterogeneity of cancer populations is explained by an equivalence principle in which multiple strategies can successfully adapt to the same barrier. This model provides a theoretical framework in which the diverse cancer genotypes and phenotypes can be understood according to their roles as adaptive strategies to overcome specific microenvironmental growth constraints.

Author affiliations

1. Robert A. Gatenby and Robert J. Gillies are at the Department of Radiology, University of Arizona, 1501 N Campbell Avenue, Tucson, Arizona 85724, USA.
2. Robert A. Gatenby is also at the Department of Applied Mathematics, University of Arizona, 1041 East Lowell Street, Tucson, Arizona 857721, USA.
3. Robert J. Gillies is also at the Department of Biochemistry & Molecular Biophysics, University of Arizona, 617 N Santa Rita Avenue, Tucson, Arizona 85721, USA.

Correspondence to: Robert A. Gatenby^1,2 Email: rgatenby@radiology.arizona.edu

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