Revisiting lactate dynamics in cancer-a metabolic expertise or an alternative attempt to survive?

Cancer cells are able to rewire their metabolism in order to support and allow rapid proliferation, continuous growth, and survival in hostile conditions, such as acidosis and hypoxia. Lactate is the final product of anaerobic glycolysis in several organisms being considered during most of the last century a dead-end waste product. In cancer context, the majority of studies on lactate have focused on its production rather than on its consumption. However, lactate has been currently proposed as a unique source of energy, a signalling molecule, and a target for cancer therapy. Cancer cells are capable of importing lactate and utilising it for energetic purposes. Indeed, lactate is a crucial substrate that fuels the oxidative metabolism of oxygenated cancer cells. In this review, we discuss the role of lactate as a key molecule in carcinogenesis, acting as a fuel for cancer cell survival, growth, and proliferation, and we describe potential therapeutic approaches to target lactate metabolism in cancer.