Gary Patti walks into his laboratory at Washington University in St. Louis with more than 20 mass spectrometers at his fingertips—an arsenal of precision instruments designed to reveal what healthy cells try to hide. He is hunting the fingerprint of hunger. Cancer cells, he has learned, are voracious in ways that healthy cells are not, and that appetite may be their undoing.
Patti is the Michael and Tana Powell Professor of Chemistry at Washington University and a professor of genetics and medicine at WashU Medicine, and he leads research at Siteman Cancer Center with a deceptively simple conviction: if we can understand how cancer cells eat differently, we might be able to starve them into submission—or at least track them before they spread.
This frontier is called cancer metabolomics, the systematic study of small molecules that tumors consume or produce as they grow. It is a relatively new field, but one with profound implications. Earlier this year, Patti and postdoctoral researcher Joe Rowles, a molecular oncology trainee in Siteman Cancer Center's Cancer Biology Pathway Program, synthesized the latest research and open questions in cancer metabolism in an article published in Nature Reviews Cancer. Their work points to two major opportunities: using metabolites as markers to identify tumors, and discovering new drugs or dietary strategies that slow growth while sparing healthy tissue.
The work is intricate because cancer cells are shape-shifters. A cancer cell growing in a laboratory dish might consume entirely different nutrients than the same cell thriving inside a human body or a mouse. What defines cancer, Patti explained, is that flexibility—the ability to adapt and survive in nearly any environment. Add to this the fact that a single tumor, like a lung cancer, contains dozens of different cell types, not all of them malignant. Some immune cells within the tumor are actually beneficial. The challenge becomes separating the metabolic fingerprint of the cancer itself from the noise of surrounding tissue.
His team is working to crack this puzzle through collaboration with WashU Medicine researchers including David Mutch, a professor of obstetrics and gynecology, and Yin Cao, an associate professor of surgery and medicine. They are conducting experiments using isotopically labeled glucose to track the dynamics of tumor metabolism directly in patients. Washington University's medical school has pioneered innovative clinical tests using isotopes, making it an ideal setting for this work.
What Patti and his colleagues have discovered is that cancer cells are not necessarily eating things that healthy cells do not eat. Rather, they are eating much faster. That accelerated appetite is the tell-tale sign. "The fact that cancer cells run distinct metabolic programs gives us two big opportunities," Patti said. The first is detection—catching tumors earlier by recognizing their unique metabolic signatures. The second is intervention: leveraging what we learn about cancer's hunger to develop new treatments or dietary strategies that could improve outcomes for patients.
The road ahead requires vast amounts of data. Metabolomics studies will need to expand across thousands of people with different diets, genetic backgrounds, and lifestyles to understand how these factors influence tumor behavior. But Patti's enthusiasm is grounded in realism and hope. "I'm very enthusiastic about the idea that we can leverage diet to improve the lives of cancer patients," he said. That conviction—that understanding how cancer feeds might help us feed better lives to those fighting it—drives the work forward.