Metabolism of Lipids in Malignant Solid Tumors Hypoxia and Drug Targets

The abrupt metabolism of glucose is a well-known hallmark of malignancy in hypoxic cancer cells, whereas little is known about lipid metabolism. Recent work has documented the role of lipid in the pathogenesis of cancer cells. As lipid are the important building blocks of cells like plasma membrane, hence needed in much more amounts in rapidly dividing cancer cells. Lipids are also utilized in energy production for emergencies like starvation, hence stored as triglycerides in the adipose tissue. Lipids also serve as important signaling molecules like steroidal hormones (testosterone, estrogen, progesterone). In normal cells, de novo fatty acid biosynthesis and dietary fats are the only sources of fatty acid in which occurs at a normal pace. Extra glucose as if 164taken by the normal cells readily converted into fats which are stored as triglycerides, for energy production, and hormonal and plasma membrane synthesis. Being rapidly dividing, cancer cells require a very high number of fatty acids for which various pathways and metabolites are reprogramed to be converted into fats. Unusual metabolites like lactate, acetate, and glutamate are converted into fatty acids. It is pertinent to mention that, unlike leukemia, microenvironment cells of solid tumors of the mammary gland, breast, and colon cancers tumors cells do not get an equal amount of nutrients and oxygen. Generally, it has been observed that cancer cells near the blood vessel take a high amount of glucose and oxygen while cancer cells away from the blood vessel get a limited supply of glucose and oxygen. Consequently, cancer cells reprogram glucose and fatty acid metabolism. Being needed in much more amounts, cancer cells took every step to enhance lipid synthesis. Hypoxia-activated hypoxia inhibited factor-1α (HIF-1α) helps the cancer cells to achieve this goal. The current chapter deals with the reprogramming of lipid metabolism under the guidance of hypoxia.