Acidity of Microenvironment as a Further Driver of Tumor Metabolic Reprogramming

n the last decade, experimental research has intensely focused on metabolic reprogramming of tumor cells, which contributes to cancer cell adaptation and survival in different and hostile microenvironments. Metabolic reprogramming consists of the switch of tumor cells from aerobic or anaerobic glycolysis to oxidative phosphorylation. A comprehensive vision of the metabolic scenario involving functionally different tumor cell subpopulations was proposed as a necessary premise to the design of new strategies of diagnosis and therapy. Special focus has been put on the role of acidosis of certain tumor regions, a very important although frequently neglected aspect. Despite the progresses in cancer therapy, the escaping of tumor cancer cells from host defense and relapse of disease still represent main issues in tumor-bearing patients. Indeed, malignant cells are provided with a tremendous plasticity that they exploit to survive, replicate and invade in stressed microenvironments. Such plasticity allows cancer cells to easily modify their properties, including metabolism, switching back and forth from aerobic or anaerobic glycolysis to oxidative phosphorylation (OxPhos). It is well ascertained that a suitable metabolic profile of cancer cells is necessary to sustain tumor growth, local invasion and distant colonization. Thus, cancer metabolism needs to be considered in view of the design of new strategies to control tumor progression.