Causes and consequences of tumour acidity and implications for treatment

Tumour cells have a lower extracellular pH (pH(e)) than normal cells; this is an intrinsic feature of the tumour phenotype, caused by alterations either in acid export from the tumour cells or in clearance of extracellular acid. Low pH(e) benefits tumour cells because it promotes invasiveness, whereas a high intracellular pH (pH(i)) gives them a competitive advantage over normal cells for growth. Molecular genetic approaches have revealed hypoxia-induced coordinated upregulation of glycolysis, a potentially important mechanism for establishing the metabolic phenotype of tumours. Understanding tumour acidity opens up new opportunities for therapy.