Cancer Cells and Glucose

By Jane Farrell

Researchers have identified a method that restricts the ability of cancer cells to consume glucose, a key source of energy.

Malignant cells consume exorbitant amounts of glucose, and shutting down this process has long been a goal of scientists. But until now, there have been no good pharmacological methods to stop cancers’ ability to uptake and metabolize glucose. In a new study published in Cell Reports, a team of University of Colorado Cancer Center researchers, led by Matthew Galbraith, PhD, and Joaquin Espinosa, PhD, have finally identified a way to restrict the ability of cancer to use glucose for energy.

Over-expression of the gene CDK8 is linked to the development of many cancers, including colorectal cancer, melanoma, and breast cancer, where it regulates pathways that drive the growth and survival of cancer cells. The researchers’ study demonstrates that CDK8 plays a critical role in allowing cancer cells to use glucose as an energy source.

Although a number of drugs aimed at blocking CDK8 activity is being developed, it is not yet clear how effective they are at treating various cancers.

When Galbraith used a sophisticated chemical genetics approach to specifically switch off CDK8 activity in colorectal cancer cells, he saw that the cells failed to take up much less glucose. He confirmed this in experiments showing that blocking CDK8 activity leads to a lower rate of glucose use.

“Because of this role of CDK8…I reasoned that the cells with impaired CDK8 activity should be more susceptible to drugs that block glycolysis, [the increased consumption of glucose],” Galbraith said. So treating cancer cells with drugs that block both CDK8 and glycolysis slowed their growth more effectively than either approach alone.

“These are very exciting discoveries,” said Espinosa, the paper’s senior author. “Combining drugs that block CDK8 activity with those that block glycolysis may enable specific targeting of cancer cells without harmful effects on normal cells.”