By Elodie Vaz | Published on February 27, 2026 | 3 min read
Cancer is
characterized by uncontrolled cell proliferation, supported by profound
metabolic reprogramming. Among the identified vulnerabilities, “glutamine
dependence” plays a central role: many tumor cells require this amino acid to
sustain protein and DNA synthesis and to maintain their energy cycle. In its
absence, proliferation halts. Yet some tumors manage to circumvent this
metabolic constraint.
A study
published on February 25 in Molecular Cell by a team from the University
of Lausanne highlights an unexpected mechanism involving vitamin B7 (biotin),
revealing a new vulnerability in tumor cells deprived of this essential
cofactor.
Understanding
escape from glutamine dependence
The team
led by Alexis Jourdain, Associate Professor in the Department of Immunobiology
(DIB) at the Faculty of Biology and Medicine (FBM) of the University of
Lausanne, set out to elucidate the mechanisms that allow cancer cells to
continue proliferating despite glutamine restriction.
Although
glutamine dependence is a well-documented vulnerability, the ability of certain
tumors to bypass it has so far limited the effectiveness of therapeutic
strategies targeting this metabolic pathway. The study therefore aimed to
identify the alternative pathways mobilized by tumor cells and the underlying
molecular determinants.
An
integrated metabolic approach
The work
was conducted by Dr. Miriam Lisci, a postdoctoral researcher in Prof.
Jourdain’s laboratory. The researchers combined functional and analytical
approaches, in collaboration with the metabolomics and proteomics platforms of
the FBM, as well as with the team of Professor Owen Skinner at Northeastern
University (United States).
The
analysis highlighted the role of carbon-rich molecules, notably pyruvate,
capable of sustaining cell division in the absence of glutamine. Experiments
dissected the enzymatic conditions required for this metabolic compensation.
Biotin
as a “Metabolic License”
The
researchers demonstrate that the use of pyruvate in this context depends on a
key mitochondrial enzyme: pyruvate carboxylase. This enzyme requires vitamin B7
to function. In the absence of biotin, pyruvate carboxylase is inactive,
blocking pyruvate utilization and preventing cell proliferation.
Biotin thus
acts as a true “metabolic license,” allowing pyruvate to fuel the cellular
energy cycle and compensate for glutamine deficiency. This mechanism reveals an
unexpected dependence of tumor cells on a micronutrient, beyond classical
energy substrates.
The study
also highlights a previously unrecognized role of the gene FBXW7,
frequently mutated in various cancers. “When FBXW7 is mutated, pyruvate
carboxylase is partially lost, pyruvate is no longer used efficiently, and the
cells become dependent on glutamine,” explains Miriam Lisci, first author of
the study, in a press release. The researchers showed that certain FBXW7
mutations identified in patients directly induce this metabolic dependence.These
findings also shed light on the limitations of some glutamine-targeting
therapies. Tumor cells can activate alternative metabolic pathways, notably via
pyruvate, to maintain proliferation.
Exploiting
tumor metabolic flexibility
By
revealing the central role of biotin and pyruvate carboxylase in the metabolic
adaptation of cancer cells, this study underscores the importance of
integrating micronutritional factors into the analysis of tumor
vulnerabilities.
“In the
longer term, this research opens new perspectives for better understanding the
metabolic vulnerabilities of cancers and for designing innovative therapeutic
strategies that take into account the high metabolic flexibility of tumor
cells, particularly by simultaneously targeting multiple metabolic pathways,”
concludes Alexis Jourdain, senior author of the study.
These
findings suggest that a combinatorial approach integrating vitamin status and
mutational profiling—particularly of FBXW7—could refine patient stratification
and improve the effectiveness of metabolic therapies. They pave the way for a
more precise exploitation of tumor nutritional dependencies at the intersection
of cell biology, oncogenetics, and precision medicine.
Read next: Prostate cancer and diet: which
eating pattern helps with prevention?
About
the Author –
Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on
human life. A registered nurse since 2010, she spent twelve years at patients’
bedsides before exchanging her stethoscope for a notebook. She now investigates
the links between environment and health, convinced that the vitality of life
cannot be reduced to that of humans alone.
