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InfoGrok Pharma, a leading pharmaceutical news and industry intelligence website is reporting that Matthew Vander Heiden and a team of researchers at Harvard University have outlined a previously unknown element of cancer cells metabolism. The scientific team found that cells can trigger an alternative biochemical pathway that speeds up their metabolism and diverts the by-products to construct new cells.

This finding could help scientists to design drugs that can effectively block cancer-cell metabolism, which would essentially starve them of the materials they need to grow and spread around the body. Assistant professor Vander Heiden has recently begun tests in mice of several such drugs.

In the same way that trees can be turned into logs to build new houses, or alternately firewood to generate heat, sugar can serve many purposes. In a regular cell, most sugar is burned up and used for energy, with little left over to build anything new. Cancer cells, on the other hand, need building blocks for new cells as well as energy.

“If you have a forest of trees, you can take all the trees and burn them and release a lot of energy, but you haven’t built anything,” says assistant professor Matthew Vander Heiden. “To build a house out of it, you need to save some logs to turn them into lumber.”

Most human cells burn a six-carbon sugar called glucose. Through an extremely long chain of reactions that require oxygen, the cells extract energy from sugar and then store it in molecular energy packets known as ATP. Cells use ATP to power a variety of functions, such as transporting molecules in and out of the cell, contracting muscle fibers and maintaining cell structure.

Glucose metabolism normally occurs in 2x stages, the first of which is known as glycolysis. It has been known for decades that cancer cells perform gylcolysis only, which is where most of the ATP is actually generated.

Mr Vander Heiden’s new study focuses on glycolysis. That pyruvate is usually fed into phase two of glucose metabolism.

“Everyone takes it for granted that this is how it works,” says Vander Heiden, who did this research as a post-doctoral fellow in the lab of Harvard Medical School Professor Lewis Cantley, author of the study paper~{“Everyone takes it for granted that this is how it works,” says Vander Heiden, who did this research as a postdoctoral fellow in the lab of Harvard Medical School Professor Lewis Cantley, author of the study paper}~“Everyone takes it for granted that this is how it works,” says Mr Vander Heiden, who did this research as a post-doctoral fellow in the lab of Harvard Medical School Professor Lewis Cantley, author of the paper}. But this brand new study shows that “there is another way it can all work, and this other way seems to be at play in proliferating cells.” That could include rapidly dividing embryonic cells as well as cancer-cells.

Scientists already knew that cancer cells replace one type of a key metabolic enzyme known as pyruvate kinase with a different one. Both PKM1 and PKM2 catalyze the very last step of glycolysis.

In a new study, the research team have found that PEP is involved in a previously unknown feedback loop. In cancer-cells, PKM2 is not active, causing PEP to actually accumulate. That excess PEP activates an enzyme called PGAM, which catalyzes an earlier step in glycolysis. When PGAM receives that extra boost, it produces even more PEP, creating a positive feedback loop in which the more PEP a cell has, the more it makes.

By far the most important result of this loop is that the cell generates a large pool of another chemical that is formed during the intermediate step of the reaction chain. The team believe that this compound is diverted into synthetic pathways such as the production of DNA, which can then become part of a new cancer cell.

The study suggests that drugs that activate PKM2 could make promising cancer treatments, says Mt Vander Heiden. If PKM2 were highly activated, cancer cells would alter the metabolism of PEP, blocking the alternative pathway and hindering the production of new building blocks.

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Tags: cancer news, pharmaceutical industry, pharmaceutical news, R&D