New Lung Cancer Drug Target Discovered

Enzyme associated with metabolic programming may lead to new treatments.

Researchers have discovered a new target in the treatment of lung cancer that may lead to novel drug development.

In a study published recently in the Journal of Clinical Investigation, researchers evaluated the Krebs cycle in the mitochondria of cells, which provides energy and building materials needed for cell growth. They specifically focused on the mitochondrial enzymes pyruvate carboxylase (PC) and glutaminase replenish carbon, which replenish the Krebs cycle.

The study utilized metabolic data collected directly from more than 120 early stage lung cancer patients to evaluate the in situ activity of these enzymes. After the patients were infused with a glucose tagged with stable heavy atoms immediately before surgery to remove tumor tissue, the PC was found to be selectively activated.

This indicated that PC expression may be an important factor in lung cancer development.

Molecular genetic tools were used to decrease the amount of PC in human lung cancer cells, which lead to a drop in cell growth, diminished ability to form colonies in soft agar, and reduced tumor growth rate in mice.

"We now know much more about metabolic reprogramming of cancerous tissues in human patients, particularly that the activation of pyruvate carboxylase is important to lung cancer cell growth and survival," lead researcher Teresa Fan, a professor of toxicology and faculty member of the Markey Cancer Center and CESB at the University of Kentucky, said in a press release. "Ultimately, figuring out how to target PC may help researchers develop new, more effective therapeutic strategies to improve upon current lung cancer treatments, which are limited and harmful."