Compared to TKI-sensitive cells, which rely on mitochondrial oxidative phosphorylation (OXPHOS) for ATP production, the resistant cell lines significantly induced hypoxic signaling and had higher levels of the glycolytic pathway pentose phosphate pathway (PPP), and fatty acid metabolic pathway.274 Increased glycolysis was also observed in sunitinib-resistant RCC cell lines and EGFR-TKIs-resistant NSCLC cell lines.275,276 Increased glycolysis may be related to the upregulation of glycolysis-related enzymes and increased glucose uptake. This evidence concerns the gene EGFR and renal cell carcinoma.