Cancer cells can trigger an alternative biochemical pathway that speeds up their metabolism and diverts the byproducts to construct new cells, says Matthew Vander Heiden, assistant professor of biology and member of the David H. Koch Institute for Integrative Cancer Research at MIT.

The finding, with researchers at Harvard University, could help scientists design drugs that block cancer-cell metabolism, essentially starving them of the materials they need to grow and spread. Vander Heiden has just begun tests in mice of several such drugs.

Scientists already knew that cancer cells replace one type of a key metabolic enzyme known as pyruvate kinase with another. Both versions of the enzyme (PKM1 and PKM2) catalyze the very last step of glycolysis, which is the transformation of a compound called PEP to the final product, pyruvate.

In the new study, the researchers found that PEP is involved in a previously unknown feedback loop that bypasses the final step of glycolysis. In cancer cells, PKM2 is not very active, causing PEP to 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.

The most important result of this loop is that the cell generates a large pool of another chemical that is formed during an intermediate step of the reaction chain. Vander Heiden believes this compound, called 3-phosphoglycerate, is diverted into synthetic pathways such as the production of DNA, which can become part of a new cancer cell. In future studies, he plans to investigate how that diversion occurs.

Their paper appeared in the Sept. 16 online edition of Science.

More info: MIT news