Abstract

If carcinogenesis occurs by somatic evolution, then common components of the cancer phenotype result from active selection and must, therefore, confer a significant growth advantage. A near-universal property of primary and metastatic cancers is upregulation of glycolysis, resulting in increased glucose consumption, which can be observed with clinical tumour imaging. We propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions. However, upregulation of glycolysis leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity. Subsequent cell populations with upregulated glycolysis and acid resistance have a powerful growth advantage, which promotes unconstrained proliferation and invasion.

Author affiliations

1. Departments of Radiology and Applied Mathematics, University of Arizona, Tucson, Arizona 85721, USA.
2. Departments of Radiology and Biochemistry and Molecular Biophysics, University of Arizona, Tucson, Arizona 85721, USA.

Correspondence to: Robert A. Gatenby¹ Email: rgatenby@radiology.arizona.edu

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