RAS oncogene activation and oxidative stress that are attributed to overproduction of ROS induce the upregulation of cancer-associated fibroblasts MCT4 (HIF-1α) in the TME, leading to decreased mitochondria function and increased rates of glycolysis, with consequent production of L-Lactate and ketone bodies that are taken up by cancer cells as an energy source for oxidative phosphorylation, thereby realizing the “metabolic symbiosis” between tumour cells and adjacent cells (229). This evidence concerns the gene HIF1A and cancer.