Metabolic alterations in lung cancer: New treatment avenues

A team of scientists from McGill University, Washington University in St. Louis, ITMO University in Saint Petersburg, Russia, and the University of Bristol in the UK have identified a new way to stop the growth of lung cancer cells by blocking their ability to use alternative sources of nutrition. The discovery was made possible by identifying the metabolic programs used by cancer cells to fuel their growth. The findings point to possible new avenues for treating lung cancer, which accounts for over one-quarter of all cancer-related deaths.

The metabolism of cancer cells is very different from normal cells. Rapid proliferation means that cancer cells have increased energy needs. This need is met using glucose as the main source of nutrition. Cancer cells use glucose at rates tens or even hundreds of times greater than that of normal cells. When glucose becomes scarce, cancer cells must switch to using alternative sources of nutrition to maintain their growth and survival.

The group chose to experiment with non–small cell lung cancer, which affects 85% to 90% of all lung cancer patients, and found that some lung cancer cells change their food preferences, switching from glucose to the amino acid glutamine, when sugar is scarce.

The researchers found that cancer cells use an enzyme known as PEPCK to reprogram cancer cell metabolism. The group also found evidence of increased PEPCK levels in tissues from lung-cancer patients, leading scientists to consider that the enzyme may play a role in the human disease. The study suggests that nutrient availability in the organism, where cancer cells must compete for glucose and other nutrients, can impact cancer progression. Researchers hope the work on PEPCK and the metabolic alterations in lung cancer cells will lead to innovations in treatment for non–small cell lung cancer.

The results of the study, “Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Metabolic Adaptation and Enables Glucose-Independent Tumor Growth,” were published in the 15 October 2015 issue of Molecular Cell, available online at www.cell.com/molecular-cell/abstract/S1097-2765(15)00659-0.