HIF1A and cancer: Lactic acid levels are related to the incidence of distant metastases.64, 65 High concentrations of lactic acid are associated with high rates of early distant metastases in cancer.66 Exogenous lactic acid can increase tumor cell motility and random migration of different cancer cell lines.67 The effect of lactic acid on metastasis mainly includes activation of matrix metalloproteinases (MMPs) and cathepsin by acidic microenvironment, up‐regulation of VEGF, HIF‐1α, and transforming growth factor‐β2 (TGF‐β2), as well as direct enhancement of cell migrative ability.66, 68, 69, 70, 71