Targeting Tissue Acidosis in Solid Tumours

Tissue acidosis happens when pH drops below 7.1-7.2 in the interstitial fluids of a tissue. This may occur during tissue injury and inflammation, but acidosis is also a well-recognised hallmark of cancerous tissue and is known to drive tumorigenesis. As a tumour grows and becomes both larger and more dense, it becomes increasingly acidic due to changes in cancer cell metabolism and diminished tissue perfusion. This acidification of the tumour tissue contributes to accelerated tumour progression and metastasis, by influencing cancer cell growth, metabolism, genomic stability and migration/invasion as well as impairing the ability of immune cells to target and destroy the tumour. Despite the obvious impact of acidosis in various pathophysiological settings our general understanding of how cells respond to acute acidosis, and which signalling pathways are mediating these responses, is still extremely vague.