Alkalinization of the tumor microenvironment: are there prospects as a therapeutic objective?

Tumor acidity is one of the hallmarks of cancer. The use of glycolysis as the main source of ATP production due to the metabolic reprogramming of cancer cells makes their intracellular pH alkaline and extracellular pH acidic. This metabolic reprogramming and acidification are part of the general defenses that allow malignant cells to survive, multiply, spread, and become resistant to therapies. Tumor acidity may also be associated with a poor prognosis for cancer patients, and clinicians should consider this when diagnosing and determining optimal treatment. On the other hand, the inversion of the pH gradient in tumors could be a weakness, which will allow the development of new promising therapies. Pharmacological inhibition of pH regulation pathways and alkalinization of the tumor appear to be prospective therapeutic options for cancer treatment. Alkalization therapy does not contradict standard treatment methods and can be used in combination to increase effectiveness. Here, we have tried to summarize the basic knowledge about tumor acidity and related potential cancer treatment options.