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tumor hypoxia
Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironements in solid tumors are in result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism.
==Changes in the glycolytic pathway==
A particular change in metabolism, historically known as the Warburg effect〔Vander Heiden, Matthew G., Lewis C. Cantley, and Craig B. Thompson. "Understanding the Warburg effect: the metabolic requirements of cell proliferation." science 324.5930 (2009): 1029-1033.〕 results in high rates of glycolysis in both normoxic and hypoxic cancer cells. Expression of genes responsible for glycolytic enzymes and glucose transporters are enhanced by numerous oncogenes including RAS, SRC, and MYC.〔Flier, Jeffrey S., et al. "Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes." Science 235.4795 (1987): 1492-1495.〕〔Osthus, Rebecca C., et al. "Deregulation of glucose transporter 1 and glycolytic gene expression by c-Myc." Journal of Biological Chemistry 275.29 (2000): 21797-21800.〕
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