Release date: 2014-06-17
Not long ago, the British "Nature" magazine published the research results of the research group of Professor Yan Ning of Tsinghua University Medical College for the first time in the world to analyze the crystal structure of human glucose transporter GLUT1. Glucose is the main "rational" of cancer cells. Because cancer cells digest glucose to produce less than 15% of normal cells, more glucose is needed. Then, can GLUT1 be used as a target to develop new drugs to inhibit its transport function, block glucose supply, and starve cancer cells? Can “starvation therapy†targeting GLUT1 treat cancer?
Therapy for "starving" cancer cells has long been available
In fact, the idea of ​​"starving" cancer cells is long gone. As early as 1971, Professor Harvard University Professor Frankman proposed this idea to cut off the blood and nutrient supply of tumor cells by neutralizing endothelial angiogenesis by monoclonal antibodies and inhibiting tumor angiogenesis. This anti-tumor therapy is called "anti-tumor angiogenesis therapy" and is also known as "starvation therapy." In 1994, the Harvard Cancer Research Center used this therapy to cure seven Lewis lung cancer mice. At present, "A+ treatment plan" for "anti-tumor angiogenesis + anti-tumor cell proliferation" has been popularized in many hospitals.
With GLUT1 as a target, the development of specific inhibitors to block the transport of glucose to cancer cells and the inability of cancer cells to survive due to lack of nutrient supply has been mentioned many years ago, and related research topics have been applied for this. . However, no clinical application of any GLUT1 inhibitor has been seen so far.
Cell and animal experiments on anticancer related inhibitors have been completed
GLUT is a generic term for "glucose transporters" embedded in mammalian cell membranes. They can act as carriers to transport extracellular glucose or other hexoses (hexoses) across the membrane into cells. Because cancer cells are mainly glycolysis (anaerobic respiration), their sugar consumption is much larger than normal cells with aerobic respiration. The "starvation therapy" targeting GLUT1 can drastically reduce the glucose intake by cancer cells. Therefore, it can selectively kill cancer cells, but has less effect on normal cells.
At present, GLUT1 carcinogens effective against lung cancer have been screened, and their evaluation results in tumor cell lines and tumor-bearing animals have been published, showing a good anti-tumor effect.
"Starving dead cancer cells" still have a distance from the actual application
Different glucose transporters are distributed in different cells, performing the same or different functions, such as monosaccharide transport, hexose transport, two-way transport, etc., and more than one type of glucose transporter is distributed on each cell, which makes GLUT1 After the function is inhibited, other glucose transporters will compensate for its function. Taking GLUT3 as an example, it is mainly distributed in neurons and placental tissues. When GLUT1 in brain tumor patients is inhibited, it can still rely on GLUT3 to take up glucose, so cancer cells can continue to grow. At the same time, GLUT1 also has a characteristic that it is easy to be induced, that is, the glucose level is low, and it is highly expressed; if the glucose level is high, it is lowly expressed, which makes the future use of the inhibitor face the problem of “water risingâ€, that is, the activity is very high. It is difficult to inhibit or easily induce drug resistance.
Although the structure of the GLUT1 protein has been resolved, structural-based drug design, development, preclinical and clinical trials have not yet begun, and there is still a lot of work to be done, including solving the above-mentioned specific and inductive problems, as well as It is too early to spend a lot of money, material and manpower, and now it is a good prospect for its anti-tumor clinical application.
Source: People's Daily
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