Compound to starve cancers of sugar-based building blocks found

WASHINGTON - Scientists have discovered a compound that could be used to starve cancers of their sugar-based building blocks.

The compound, called a glutaminase inhibitor, has been tested on laboratory-cultured, sugar-hungry brain cancer cells and, the scientists say, may have the potential to be used for many types of primary brain tumors.

The Johns Hopkins scientists warned that glutaminase inhibitors have not been tested in animals or humans, but their findings may spark new interest in the glutaminase pathway as a target for new therapies.

Glutaminase is an enzyme that controls how glucose-based nutrients are converted into the carbon skeleton of a cell.

Additional enzymes that help construct the so-called “bricks” of the carbon skeleton are controlled by a gene called IDH1. In some brain cancer cells, IDH1 is mutated and the resulting enzyme grinds up the bricks into nutrients that feed cancer cells.

“Cancer cells with mutated IDH1 become addicted to the glutaminase pathway, and this pathway may represent an Achilles’ heel of cancer cells,” said Chi Dang of the Johns Hopkins University.

“To combat cancer, we might block the flow of materials that help create the bricks, starting with glutaminase,” said Dang.

The Johns Hopkins scientists and a team of chemists and geneticists at Princeton University used a glutaminase-blocking agent on cells engineered to have IDH1 mutations. The compound, called BPTES, reduced growth of the cancer cells by 30 percent.

“The glutaminase inhibitor we tested does not completely stop cancer cell growth, but slows it down,” said Gregory Riggins, of Johns Hopkins.

Riggins identified BPTES’ anticancer potential after screening many compounds for their glutaminase-blocking activity.

Dang said, “We can envision a day when patients who have IDH1 mutations are given a glutaminase inhibitor in addition to therapies that target other genomic aspects specific to their cancer.”

Their findings were published online November 2 in Cancer Research. (ANI)