Why do some anti-glutamine therapies fail? A new study uncovers a hidden metabolic workaround involving pyruvate, biotin, and mutations in the FBXW7 gene.
Scientists at the University of Lausanne (Unil) have uncovered a cellular mechanism that reveals a hidden weakness in tumor cells when they are deprived of vitamin B7.
All living cells must constantly adjust to changes in nutrient supply. This flexibility is essential for survival. However, some cells develop a strong reliance on glutamine, an amino acid that plays a central role in metabolism. Glutamine supplies critical components needed to build proteins and DNA. When it is unavailable, cells are unable to continue dividing.
Cancer cells are a prime example. Their reliance on this nutrient, often described as “glutamine addiction,” is considered a well-known weakness. Even so, many tumors find ways to overcome this dependence. In research published in the journal Molecular Cell, a team led by Alexis Jourdain, assistant professor in the Department of Immunobiology (DIB) at Unil’s Faculty of Biology and Medicine (FBM), clarifies biological processes that were not fully understood until now.
How Cells Bypass Glutamine Dependence
The study was spearheaded by Dr. Miriam Lisci, a postdoctoral researcher in Prof. Jourdain’s lab. The researchers focused on carbon-rich molecules, especially pyruvate, and found that these compounds allow cells to keep dividing even when glutamine levels are low.
Their experiments showed that this workaround depends on a mitochondrial enzyme known as pyruvate carboxylase. For this enzyme to operate, it must bind to vitamin B7 (or biotin). Without vitamin B7, the enzyme remains inactive, and cell growth comes to a halt.
In this context, biotin functions as a “metabolic license,” making it possible for pyruvate to enter the cell’s energy-producing pathways and compensate for the absence of glutamine.
The key role of the FBXW7 gene
The team also identified a new function for FBXW7, a gene already linked to many types of cancer. “When FBXW7 is mutated — a situation that is frequent in certain cancers — pyruvate carboxylase partially disappears, pyruvate can no longer be used efficiently, and cells become dependent on glutamine,” explains Miriam Lisci, first author of the article.
The researchers further demonstrated that specific FBXW7 mutations observed in patients directly cause this metabolic dependence. These findings were made possible through collaborations with the FBM’s metabolomics and proteomics platforms, as well as with Prof. Owen Skinner’s team at Northeastern University in the United States.
The study also sheds light on why some treatments designed to block glutamine metabolism do not succeed. Cancer cells can switch to alternative metabolic routes, allowing them to survive despite therapy. “In the longer term, this 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,” concludes Alexis Jourdain, senior author of the study.
Reference: “Functional nutrient-genetic profiling reveals biotin and FBXW7 are essential to bypass glutamine addiction” by Miriam Lisci, Fanny Vericel, Yifan Liu, Hector Gallart-Ayala, Julijana Ivanisevic, Owen S. Skinner and Alexis A. Jourdain, 25 February 2026, Molecular Cell.
DOI: 10.1016/j.molcel.2026.02.002
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2 Comments
Fascinating research. It’s a good reminder of how complex nutrient–cell interactions really are — especially in cancer metabolism.
Important to say this doesn’t mean people should start supplementing (or avoiding) biotin on their own. These pathways are highly specific to tumour biology and genetic mutations.
It does show how nutrients like vitamin B7 play very precise roles at a cellular level. In everyday supplementation, balance matters — not mega-dosing individual vitamins in isolation.
Arbor Vitamins focus on sensible, physiologically appropriate levels rather than high single-nutrient formulas. Science like this is exactly why nuance is important.
thanks fpr this