Targeting cancer cell metabolism

cancer is caused by the uncontrolled proliferation of cells cancer cells are hungry in order to meet their demand for the nutrients and cellular building blocks that enable them to grow and divide rapidly their metabolism changes new insights into these processes have sparked interest in developing drugs that target the unique metabolic characteristics of cancer cells such drugs have the potential to treat cancers arising from many different tissues while leaving normal cells relatively unaffected the altered metabolism of cancer cells includes an increased uptake of nutrients such schoo COEs and glutamine also they start to metabolize glucose in a slightly different way a phenomenon called the Warburg effect in all cells glucose is broken down in several steps to pyruvate in normal cells most of the pyruvate enters the citric acid cycle in the mitochondria which effectively act as the energy factories of the cell in this way most of the glucose that is taken up is completely oxidized to carbon dioxide in the 1920s Otto Warburg discovered that cancer cells unlike most healthy cells metabolize most of their glucose using biochemical pathways that do not require oxygen regardless of whether oxygen is available excess glucose is taken up and like in normal cells broken down to pyruvate however instead of entering the citric acid cycle most of the pyruvate is converted to lactate which is secreted from the cell it is still controversial why tumor cells employ this relatively inefficient way of extracting energy from glucose one theory is that the process reflects a metabolic program that cells use to convert nutrients into the building blocks of matter molecules cells can be viewed as molecular factories and glycolysis is not the only aspect of the cells metabolism the resulted in cancer cells cancer cells undergo a general shift and catabolic two anabolic metabolism in order to produce the greatly increased amounts of proteins nucleic acids and liquids they need to support their high rates of proliferation cancer cells also take up amino acids amongst these glutamine is of particular importance it act as a key source of nitrogen which is required for nucleotide and new amino acid synthesis in some cancer cells due to meat also acts as a critical source of carbon which is required for replenishing the components of the citric acid cycle many anti-cancer drugs on the market have metabolic targets in the cells although for a large proportion of them the metabolic target was only recognized long after the drug was developed for example the widely used chemotherapy drugs 5-fluorouracil and gemcitabine interfere with DNA synthesis today there are a multitude of approaches in development that aim to target different aspects of cancer cell metabolism for instance scientists are exploring the possibility of blocking glutamine to interrupt the supply of carbon and nitrogen they're also considering other enzyme targets that might limit the use of nutrients to make key building blocks some strategies are aimed at interfering with the high rates of glucose metabolism and lactate secretion as described by otto warburg anti-cancer approaches targeting tumor metabolism faced many challenges a major one is finding the therapeutic window to prevent toxicity to normal tissues however it's become clear that the genetic changes associated with cancer can create addictions to specific metabolic pathways which can be therapeutically exploited moreover cancer cells can be more sensitive to metabolic perturbations than normal cells due to the loss of cell cycle checkpoints a better understanding of how metabolism is altered in specific genetic context that lead to cancer will help scientists identify enzymes or combinations of enzymes to target for intervention and hopefully allow the creation of more effective anti-cancer drugs

Channel: nature video

Views: 645,893

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Keywords: Cell (Anatomical Structure), Metabolism (Literature Subject), Health (Industry), Cancer (Disease Or Medical Condition), Nature Reviews Drug Discovery, NRDD, Nature, Nature Video, cell metabolism, cancer cell metabolism, cancer metabolism, Cancer Cell, Medicine (Field Of Study), animation, 3D, treatment

Id: kYmLQP2M-qo

Length: 5min 40sec (340 seconds)

Published: Fri Nov 21 2014