A recent study by the University of Kentucky Markey Cancer Center and the UK’s Center for Environmental and Systems Biochemistry researchers has shown that targeting an essential enzyme and its metabolic programming could potentially result in novel drug development for lung cancer treatment.
In order to keep up with the high energetic demands of excessive growth, cancer cells naturally alter their metabolism. One of these alterations occurs at the level of mitochondria, the cellular organ responsible for the Krebs cycle used to supply energetic and building supplements for cell growth. There are two important enzymes responsible for replenishing carbon to this cycle: pyruvate carboxylase (PC) and glutaminase.
In this novel study, published in the Journal of Clinical Investigation, the authors gathered metabolic data from over 120 human lung cancer patients, measuring the enzymatic activity of both PC and glutaminase in patients who were at an early stage of the disease.
The researchers used a glucose molecule loaded with stable heavy atoms and infused it onto patients before they underwent surgical tumor resection. The results showed that PC was selectively activated in these patients, demonstrating it could play an important role in lung cancer development.
After reducing the levels of PC in human lung cancer cells, the team observed these cells were not able to proliferate at high levels or form aggressive colonies anymore. Moreover, in mice models of lung cancer, there was a significant decrease in tumor growth in animals harboring cancerous cells.
Importantly, blocking PC also induced important modifications in the central metabolism of the cell, suggesting a role for this enzyme in early stages of metabolic reprogramming.
“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,” study author Dr. Teresa Fan, UK professor of toxicology and faculty member of the Markey Cancer Center and CESB at the University of Kentucky, said in a news 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.”