**5. Conclusions**

found that cancer cells expended much more glucose to generate lactic acid than normal

**Figure 6.** Schematic representation of the connecting glucose and lipid metabolism in cancer cells.

cells have an alteration of glucose metabolism. Warburg [99] considered that these defects of respiration caused a form of metabolic disturbance that was significant for carcinogenesis. After Warburg, many biologists attempted to clarify the molecular basis of aerobic glycolysis occurring in tumor cells. Accumulated evidence suggested that many cancer-related genes, such as p53, c-Myc, and Ras, are all associated with modulation of the Warburg effect [104]. As a master regulator of the cancer hypoxic response, hypoxia-inducible factor (HIF)-1 plays very important roles in modulating aerobic glycolysis to meet the biosynthetic demands of cancer cells and to protect them from damage due to hypoxic stress [105]. Warburg theorized that cancer cells shift from oxygen-dependent efficient ATP production via OXPHOS in mitochondria to the less efficient cytoplasmic glycolysis. As a result, cancer cells need to burn up more glucose to maintain their energy requirements for survival and growth. It has been reported that HIF-1α activates the expression of glucose transporter 1, 3 (Glut1, Glut3) under hypoxic conditions [106, 107], which acquires sufficient glucose uptake by tumor cells. We also examined HIF, and details can be found in Chapter 10 of the InTech book *Tumor Microenvironment and Myelomonocytic Cells* [108]. Although clarification of glucose metabolism is considered vital for understanding energy metabolism in oral

cancer, lipid metabolism has also been receiving attention recently (**Figure 6**).

Lipids are composed of phospholipids, triglycerides, cholesterol esters, cholesterol, fatty acids, sphingolipids, and other molecules, which are critical components of cellular membranes

sufficiency. This finding was the first indication that cancer

cells even under conditions of O2

94 Prevention, Detection and Management of Oral Cancer

**4.2. Lipid metabolism in oral cancer**

Unlike surgery, chemotherapy, and radiotherapy, which can have serious side effects on the human body, the use of agents that have no such side effects, such as TRAIL, cimetidine, mangostin, and antibodies, for cancer therapy mobilizes and regulates systemic functions, enhancing the body's ability to fight cancer. Therefore, these medicines may be more appropriate for patients with inoperable advanced cancer, those in periods of chemotherapy intermission, or those during postoperative recovery. There has been an increased emphasis on such agents for prevention of cancer and inhibition of cancer metastasis. There has been an impressive renaissance in the search for semi-synthetic drugs or derivatives from natural compounds. Progress in this regard not only adds to the chemical bank but also leads to a better comprehension of the chemical basis of treatments lacking side effects for the treatment of cancers using drugs obtained from natural sources.

Further studies will be required to establish a strategy for basic molecular and clinical approaches for effective oral cancer therapy, which should be tailored to individual patients.
