Researchers in the Schools of Medicine and Engineering at Vanderbilt University have discovered a proteomic "signature" from the airways of heavy smokers that could lead to better risk assessment and perhaps new ways to stop lung cancer before it starts.

Their findings, reported recently in the journal JCI Insight, are based on the observation that otherwise normal-looking cells in the epithelial lining of the lungs of heavy smokers and others at high risk for lung cancer undergo the same kind of "metabolic reprogramming" as do cancer cells.

To produce the extra lipids, nucleotides and amino acids they need to proliferate rapidly, cancer cells have to consume a lot of fuel, namely glucose. They essentially reverse the normal glucose-production cycle and "reprogram" their metabolism to increase uptake of glucose as well as glutamine, another quick-energy fuel.

The researchers discovered that normal cells in the lungs of heavy smokers do the same thing. The next step is to confirm that metabolic reprogramming is a "prerequisite for uncontrolled growth," said Jamshedur Rahman, PhD, research assistant professor of Medicine.

If so, metabolic reprogramming "would be a biomarker for risk," as well as an avenue for prevention, by targeting enzymes in metabolic pathways that lead to cancer, said senior author Pierre Massion, MD, Cornelius Vanderbilt Professor of Medicine and Cancer Biology.

"We're far from that target," said Massion, who directs the Cancer Early Detection and Prevention Initiative in the Vanderbilt-Ingram Cancer Center (VICC). "But this is a really exciting time for us."

Massion said the research could not have been done without major support from the National Cancer Institute (grant number CA152662) or the contributions of scientists across the University, including the paper's first authors, Rahman and research fellow Xiangming Ji, PhD.

Daniel Liebler, PhD, Ingram Professor of Cancer Research and director of the Jim Ayers Institute for Precancer Detection and Diagnosis at VICC, helped determine the "proteome," the unique set of proteins expressed in the lungs of cancer patients and those at high-risk for developing the disease.

Jamey Young, PhD, associate professor of Chemical and Biomolecular Engineering, developed software that enabled the researchers to track how glutamine was being used by epithelial cells.

Despite decades of attempts to thwart it, lung cancer remains the No. 1 cancer killer in the world, said Massion, who chairs the Lung Cancer Cooperative Group in the Early Detection Research Network, part of the National Cancer Institute.

"It's hard to stop a train that's going 200 miles an hour," he said. "We want to prevent this from gaining speed and, if possible, to ever get on the track."