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The notion that invasive cancer is a product of somatic evolution is a well-established theory that can be modelled mathematically and demonstrated empirically from therapeutic responses. Somatic evolution is by no means deterministic, and ample opportunities exist to steer its trajectory towards cancer cell extinction. One such strategy is to alter the chemical microenvironment shared between host and cancer cells in a way that no longer favours the latter. Ever since the first description of the Warburg effect, acidosis has been recognised as a key chemical signature of the tumour microenvironment. Recent findings have suggested that responses to acidosis, arising through a process of selection and adaptation, give cancer cells a competitive advantage over the host. A surge of research efforts has attempted to understand the basis of this advantage and seek ways of exploiting it therapeutically. Here, we review key findings and place these in the context of a mathematical framework. Looking ahead, we highlight areas relating to cellular adaptation, selection and heterogeneity that merit more research efforts in order to close-in on the goal of exploiting tumour acidity in future therapies.

Type

Journal article

Journal

Cancer and Metastasis Reviews

Publisher

Springer (part of Springer Nature)

Publication Date

22/11/2021

Addresses

Wiktoria Blaszczak, University of Oxford, Physiology, Anatomy and Genetics, Parks Road, OX13PT, OX13PT, Oxford, Pawel Swietach, University of Oxford, Physiology, Anatomy and Genetics, Parks Road, Oxford, OX13PT

Keywords

acidosis, cancer, metabolism, pH, acid-base, variation, adaptation, selection, phenotype, evolution