A groundbreaking study from the University of Lausanne (Unil) has unveiled a novel metabolic mechanism that exposes a critical vulnerability in tumor cells, specifically when they face deprivation of vitamin B7, also known as biotin. This discovery sheds light on the adaptive capacity of cancer cells and introduces promising avenues for more effective therapeutic interventions targeting their metabolic flexibility.
Cellular survival and proliferation hinge upon the ability to adapt to changing nutritional landscapes. Among these nutrients, glutamine stands out as a pivotal amino acid essential for various biosynthetic processes. Glutamine not only supplies carbon and nitrogen for the synthesis of proteins and nucleotides but also supports energy generation and redox balance. Many tumor cells exhibit a phenomenon termed “glutamine addiction,” reflecting their heightened reliance on this amino acid for fueling their rampant proliferation. However, this dependency is not absolute; some cancer cells employ alternative metabolic routes to bypass glutamine scarcity, complicating treatment strategies aimed at exploiting this weakness.
The study, published in Molecular Cell and led by Assistant Professor Alexis Jourdain from Unil’s Department of Immunobiology, advances our understanding of how cancer cells circumvent glutamine addiction. Dr. Miriam Lisci, a postdoctoral researcher in Jourdain’s laboratory, spearheaded research that highlights the indispensable role of carbon-rich metabolites, particularly pyruvate, in sustaining cell division when glutamine is absent. Pyruvate, a key intermediate in cellular metabolism, can enter the tricarboxylic acid (TCA) cycle to replenish biochemical intermediates and maintain energy production, effectively compensating for glutamine shortage.
Central to this metabolic compensation is a mitochondrial enzyme known as pyruvate carboxylase. This enzyme catalyzes the carboxylation of pyruvate to oxaloacetate, a critical anaplerotic reaction replenishing TCA cycle intermediates. Importantly, pyruvate carboxylase requires vitamin B7 (biotin) as a cofactor to execute its function. In the absence of biotin, this enzyme becomes inactive, halting the compensatory metabolic pathway and stalling cellular proliferation. This finding positions vitamin B7 as a “metabolic license,” a necessary molecular determinant enabling pyruvate-driven metabolism that can override glutamine dependence in cancer cells.
Further deepening the complexity of glutamine addiction, the researchers uncovered a hitherto unappreciated role for the FBXW7 gene in this metabolic interplay. FBXW7 is recognized as a tumor suppressor gene, frequently mutated in various cancer types. The study reveals that mutations in FBXW7 lead to a reduction in pyruvate carboxylase levels, impairing the ability of tumor cells to utilize pyruvate efficiently. As a consequence, mutant FBXW7 cells remain locked in a state of glutamine addiction, unable to activate the biotin-dependent metabolic bypass. This gene-nutrient interaction fundamentally reframes how genetic mutations intersect with metabolic adaptability in cancer.
Importantly, the team demonstrated that specific FBXW7 mutations identified in cancer patients directly induce this metabolic vulnerability. This link, established through a combination of metabolomics and proteomics analyses conducted in collaboration with the University’s specialized platforms and international partners, underscores the translational relevance of these findings. Understanding patient-specific genetic backgrounds could guide precision therapies targeting metabolic dependencies unique to tumor genotypes.
These insights offer a compelling explanation for why some therapeutic strategies targeting glutamine metabolism have underperformed in clinical settings. Cancer cells’ capacity to engage alternative metabolic pathways, such as the pyruvate carboxylase-dependent route enabled by biotin, confers resistance to glutamine deprivation. Thus, single-pathway targeting approaches may be insufficient given the metabolic plasticity inherent to tumor cells.
Looking ahead, Prof. Jourdain and his colleagues emphasize the potential for designing innovative treatment regimens that simultaneously target multiple metabolic axes. Such combinatory approaches could exploit the metabolic inflexibility imposed by FBXW7 mutations or vitamin B7 deprivation, potentially overcoming resistance mechanisms. This multi-targeted strategy represents a promising frontier in oncology, aiming to cut off cancer cells’ escape routes by anticipating and blocking adaptive metabolic rewiring.
The broader implications of this research extend beyond cancer, touching on fundamental principles of cellular metabolism and nutrient sensing. The concept of “metabolic licensing” by vitamins like biotin introduces a nuanced understanding of how micronutrients influence enzymatic activity and metabolic pathway choice, with potential relevance in diverse physiological and pathological contexts.
Altogether, this pioneering study not only delineates a critical metabolic dependency shaped by the interplay of nutrient availability and genetic background but also charts a path toward more effective, metabolism-informed cancer therapies. By exposing how pyruvate carboxylase and biotin serve as lynchpins in bypassing glutamine addiction, it opens novel horizons for exploiting metabolic vulnerabilities in tumors notoriously adept at evading treatment.
With these advances, the fight against cancer gains a powerful new tool: deciphering and manipulating the metabolic “licenses” that cancer cells rely on to thrive under nutrient stress. This elegant integration of genetics, metabolism, and enzymology exemplifies the cutting-edge research necessary to unravel and ultimately outmaneuver the complexities of tumor biology.
Subject of Research: Tumor cell metabolism, glutamine addiction, vitamin B7 (biotin), pyruvate carboxylase, FBXW7 gene mutations, metabolic flexibility in cancer
Article Title: Functional nutrient-genetic profiling reveals biotin and FBXW7 are essential to bypass glutamine addiction
News Publication Date: 25-Feb-2026
Web References:
Molecular Cell DOI: 10.1016/j.molcel.2026.02.002
Department of Immunobiology, University of Lausanne: https://www.unil.ch/fbm/en/home/menuinst/recherche/ssf/dib.html
Jourdain Lab: https://www.jourdainlab.org/
FBM Metabolomics Platform: https://wp.unil.ch/metabolomics/
FBM Proteomics Platform: https://wp.unil.ch/paf/
Keywords: Cancer metabolism, glutamine addiction, pyruvate carboxylase, vitamin B7, biotin, FBXW7 gene, metabolic flexibility, tumor vulnerabilities, mitochondrial enzymes, metabolic licensing, metabolic pathways, targeted therapies
Tags: cancer cell nutrient adaptationcancer cell proliferation mechanismsglutamine addiction in cancer cellsglutamine alternative metabolic pathwaysmetabolic flexibility in tumorsmetabolic interventions in oncologynovel cancer therapy strategiesrole of vitamins in cancer treatmenttherapeutic targets for cancer metabolismtumor cell metabolic vulnerabilityUniversity of Lausanne cancer researchvitamin B7 biotin cancer metabolism
