High amount of aerobic glycolysis (also known as the Warburg effect) distinguishes cancer cells from normal cells. The conversion of glucose to lactate rather than metabolizing it in the mitochondria through oxidative phosphorylation, (which can also occur in hypoxic normal cells) persists in malignant tumor despite the presence of oxygen. This process normally inhibits glycolysis which is also known as Pasteur effect. One of the reasons it is observed is because of the malfunction of mitochondria. Although ATP production by glycolysis can be more rapid than by oxidative phosphorylation, it is far less efficient in terms of ATP generated per unit of glucose consumed. Rather than oxidizing glucose for ATP production, glucose in cancer cells tends to be used for anabolic processes, such as ribose production, protein glycosylation and serine synthesis. This shift therefore demands that tumor cells implement an abnormally high rate of glucose uptake to meet their increased needs.
As neoplastic cells accumulate in three-dimensional multicellular masses, local low nutrient and oxygen levels trigger the growth of new blood vessels into the neoplasm. The imperfect neovasculature in the tumor bed is poorly formed and is inefficient. It therefore, causes nutrient and hypoxic stress (or a state of hypoxia). In this regard, cancer cells and stromal cells can symbiotically recycle and maximize the use of nutrients. Hypoxic adaptation by cancer cells is essential for survival and progression of a tumor. In addition to cell-autonomous changes that drive a cancer cell to proliferate and contribute to tumorigenesis, it has also been observed that alterations in whole-organism metabolism such as obesity are associated with heightened risks for a variety of cancers.