The impact of tumour pH on cancer progression: strategies for clinical intervention

Carol Ward; James Meehan; Mark E Gray; Alan F Murray; David J Argyle; Ian H Kunkler; Simon P Langdon

doi:10.37349/etat.2020.00005

The impact of tumour pH on cancer progression: strategies for clinical intervention

Explor Target Antitumor Ther. 2020;1(2):71-100. doi: 10.37349/etat.2020.00005. Epub 2020 Apr 28.

Authors

Carol Ward¹, James Meehan¹, Mark E Gray², Alan F Murray³, David J Argyle², Ian H Kunkler¹, Simon P Langdon¹

Affiliations

¹ Cancer Research UK Edinburgh Centre and Edinburgh Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, EH4 2XU Edinburgh, UK.
² Royal (Dick) School of Veterinary Studies and Roslin Institute, University of Edinburgh, Easter Bush, EH25 9RG Midlothian, UK.
³ School of Engineering, Institute for Integrated Micro and Nano Systems, EH9 3JL Edinburgh, UK.

Abstract

Dysregulation of cellular pH is frequent in solid tumours and provides potential opportunities for therapeutic intervention. The acidic microenvironment within a tumour can promote migration, invasion and metastasis of cancer cells through a variety of mechanisms. Pathways associated with the control of intracellular pH that are under consideration for intervention include carbonic anhydrase IX, the monocarboxylate transporters (MCT, MCT1 and MCT4), the vacuolar-type H⁺-ATPase proton pump, and the sodium-hydrogen exchanger 1. This review will describe progress in the development of inhibitors to these targets.

Keywords: Tumour pH; acidosis; carbonic anhydrase IX; hypoxia; inhibitor; monocarboxylate transporter 1; monocarboxylate transporter 4; sodium-hydrogen exchanger 1; vacuolar-type H+-ATPase proton pump.

Publication types

Review