Researchers at the University of Lausanne have identified a metabolic weak spot in tumors: block vitamin B7, and cancer cells lose their ability to compensate when starved of glutamine, an amino acid they depend on for survival.
The discovery, published in Molecular Cell, reveals how certain cancers adapt to nutrient scarcity by pivoting to alternative energy sources. That flexibility, which has made many cancer therapies fail, may finally have a pressure point.
Cancer cells are notoriously dependent on glutamine. This amino acid is essential for building proteins and DNA, and tumors have evolved to rely on it heavily. But when glutamine runs low, many cancers don't collapse. Instead, they shift their metabolism to carbon-rich molecules like pyruvate, which serve as a workaround to keep growth and division going.
The Lausanne team, led by assistant professor Alexis Jourdain and postdoctoral researcher Miriam Lisci, focused on the enzyme that enables this metabolic switch: pyruvate carboxylase. This enzyme sits inside mitochondria and has a critical requirement: it needs vitamin B7, also known as biotin, to function at all.
Without biotin, pyruvate carboxylase shuts down. Cells lose their escape route around glutamine starvation. Growth halts. In effect, biotin acts as a metabolic gatekeeper that cancer cells cannot bypass.
The research also exposed a new vulnerability tied to the FBXW7 gene, which is frequently mutated in human cancers. When FBXW7 is mutated in the specific ways researchers found in cancer patients, the cell degrades its supply of pyruvate carboxylase. With less of the enzyme available, cells become trapped: they cannot use pyruvate efficiently and fall back into glutamine dependence.
"When FBXW7 is mutated, pyruvate carboxylase partially disappears, pyruvate can no longer be used efficiently, and cells become dependent on glutamine," Lisci explained in the study.
The finding helps explain a stubborn problem in cancer treatment. Many therapeutic strategies have tried to starve tumors by blocking glutamine metabolism. Yet these drugs often fail because cancers simply switch to alternative pathways and survive anyway. The new work suggests that hitting multiple metabolic routes at once, rather than targeting a single weakness, may be necessary.
Jourdain noted that the research "opens up new avenues for better understanding the metabolic vulnerabilities of cancers and for designing innovative therapeutic strategies that take into account the great metabolic flexibility of tumor cells, notably by targeting several metabolic pathways simultaneously."
The work was made possible through collaborations with metabolomics and proteomics platforms at the University of Lausanne's Faculty of Biology and Medicine, as well as partnerships with researchers at Northeastern University in the United States.
Author Jessica Williams: "This is the kind of specificity that cancer research has been missing: a concrete metabolic chokepoint that tumors cannot simply work around alone."
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