Found a new target for cancer drugs

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Найдены новые мишени для лекарств от ракаScientists blocked LDHA in melanoma cells.

In the early twentieth century, the German physiologist Otto Warburg found that cancer cells eat not as healthy. Normally, the cell gets energy in the process of aerobic decomposition of glucose, in which one monosaccharide molecule yields 36 cell units of the fuel – molecules of adenosine triphosphate (ATP). Cancer cells use the mechanism of anaerobic glycolysis, which yields only two molecules of ATP.

This phenomenon, known as Warburg effect, in theory, allows you to “starve” a cancer cell starvation: you need only to block substances that are important for anaerobic process. However, so far attempts to do this were not too successful. It was found that from a wide range of enzymes involved in anaerobic glycolysis for cancer cells is the most important lactatdehydrogenase A (LDHA). A substance which could block this enzyme in the living body, still not found.

Scientists from the Medical research Institute of Stanford-Burnham (USA) found that even if lactate dehydrogenase And eliminated from the cell metabolism of skin tumor (melanoma), after a while glycolysis resumes – and again the cancer cell obtains energy, grows and divides. Doctors also found that the replacement LDHA comes another substance, the transcription factor ATF4: a mutant cell soon switches to a signaling pathway involving this substance and renews life.

After scientists blocked LDHA in melanoma cells, the latter ceased to use ATP as source of energy: instead, they began “to eat” amino acid glutamine. In the cells significantly increased production of ATF4, increased intake of glutamine into the cell from the outside. The influx of amino acids, in turn, activated the production of the enzyme mTOR – regulator of cell growth and survival, allowing the cells continued to grow.

The head of research Gaurav Patria (Patria Gaurav) and his colleagues believe that the simultaneous impact on the LDGA and mTOR can stop the anaerobic glycolysis in melanoma cells, their growth and division, and even cause death of cancer cells. It makes sense to also try to block other enzymes involved in glutamine metabolism and of the ERK signaling pathway, for which there are efficient inhibitors.

Data obtained Patria and his colleagues, not only suggesting a new target for future drugs for melanoma, but also help to understand the reasons for the existence of the Warburg effect. “Perhaps the fact that cancer cells are easier to obtain ATP, and use for the growth of amino acids, and the rejection of aerobic glycolysis due to this,” explains Patria.

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