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Tumour acidosis: from the passenger to the driver's seat.

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Corbet, Cyril [UCL] Feron, Olivier [UCL]

The high metabolic demand of cancer cells leads to an accumulation of H(+) ions in the tumour microenvironment. The disorganized tumour vasculature prevents an efficient wash-out of H(+) ions released into the extracellular medium but also favours the development of tumour hypoxic regions associated with a shift towards glycolytic metabolism. Under hypoxia, the final balance of glycolysis, including breakdown of generated ATP, is the production of lactate and a stoichiometric amount of H(+) ions. Another major source of H(+) ions results from hydration of CO2 produced in the more oxidative tumour areas. All of these events occur at high rates in tumours to fulfil bioenergetic and biosynthetic needs. This Review summarizes the current understanding of how H(+)-generating metabolic processes segregate within tumours according to the distance from blood vessels and inversely how ambient acidosis influences tumour metabolism, reducing glycolysis while promoting mitochondrial activity. The Review also presents novel insights supporting the participation of acidosis in cancer progression via stimulation of autophagy and immunosuppression. Finally, recent advances in the different therapeutic modalities aiming to either block pH-regulatory systems or exploit acidosis will be discussed.

Document type Article de périodique (Journal article)
Access type Accès restreint
Publication date 2017
Language Anglais
Journal information "Nature Reviews. Cancer" - Vol. 17, no.10, p. 577-593 (2017)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 1474-175X
e-issn 1474-1768
Publication status Publié
Affiliations UCL - SSS/IREC - Institut de recherche expérimentale et clinique
UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
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Permanent URL http://hdl.handle.net/2078.1/187840