药理学专题-肿瘤细胞的代谢改变与抗肿瘤药物靶点的发现-邢美春

more nutrient hungry and excrete more waste products
resulting in a build-up of metabolites inside the cell and the formation of a more hostile environment outside the cell
Agents used in combination with glycolysis inhibitors include both chemotherapy and radiotherapy
do not seem to have as significant an effect on tumour growth as monotherapy
➢ Advantages (C–E). The altered metabolism of cancer cells is likely to imbue them with several proliferative and survival advantages, ➢ Potential Liabilities (F and G). This altered metabolism, however, may also confer several vulnerabilities on cancer cells.
The regulation of glucose metabolism in cancer cellse enters the cell through a glucose transporter, it is phosphorylated by HK to glucose-6-phosphate, which is further metabolized by glycolysis to pyruvate in the cytosol. Under aerobic conditions, normal cells use pyruvate dehydrogenase (PDH) to convert most pyruvate to acetyl-CoA. The acetyl-CoA is then oxidized via the TCA cycle, providing sources of ATP synthesis. In contrast, the metabolic pathways of glucose utilization in cancer are changed from ATP generation by oxidative phosphorylation to ATP generation through glycolysis. Also, for cell proliferation to occur, cancer cells require the synthesis of new macromolecules (for example, nucleic acids, lipids, proteins). Key enzymes that may be promising targets for cancer therapy are highlighted in red. TCA enzymes that are known to be mutated in cancer are shown in purple: IDH2, SDH, and FH.
Miran Jang et al. Cancer cell metabolism: implications for therapeutic targets. Experimental & Molecular Medicine (2013) Oct 4;45:e45
2.Targeting glycolysis
have been used as chemotherapeutic agents for several years
But can resensitize tumors to other chemotherapeutic agents (such as paclitaxel)
inhibits the proliferation of tumor cells and promotes their differentiation；but were found to be toxic or raised an immune reaction
lipids and nucleotides, as well as energy in the form of ATP
Warburg effect
➢ Drivers (A and B). The metabolic derangements in cancer cells may arise either from the selection of cells that have adapted to the tumor microenvironment or from aberrant signaling due to oncogene activation.
THE CHANGES IN METABOLISM IN TUMOR AND THE FINDING OF NEW TARGETS
ABOUT METABOLIC ALTERATION OF CANCER CELL
higher proliferative rates
Metabolic activities in cancer cells are dramatically fast.
In order to divide, a cell needs to both increase its size and replicate its DNA — processes that are hugely metabolically demanding and which require large quantities of proteins,