ArticleNature communications2025
PPARα-mediated lipid metabolism reprogramming supports anti-EGFR therapy resistance in head and neck squamous cell carcinoma.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed.
- Pan-tumor spatial transcriptomics reveals conserved properties of tumor organization.Cell reports. Medicine · 2026Article
- Metabolic and Clinical-Nutritional Correlation Patterns in Relation to 3-Year Disease-Free Survival in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Preliminary Analysis.International journal of molecular sciences · 2026Article
- Si Ni Powder enhances chemotherapy efficacy in sleep-deprived breast cancer via modulation of the tumor microenvironment.Translational cancer research · 2026Article
- Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects.Journal of molecular histology · 2026Review
- Reciprocal signaling-metabolic crosstalk between fibroblasts and tumor cells drives cetuximab tolerance in head and neck cancers.Journal of experimental & clinical cancer research : CR · 2026Article
- ACOT9, a mitochondrial metabolism-related gene, promotes ROS-associated epithelial remodeling in laryngeal squamous cell carcinoma.Journal of translational medicine · 2026Article
- Targeting STAT3-mediated lipid metabolism reprogramming overcomes chemoresistance in acute myeloid leukemia.Cell death & disease · 2026Article
- Integrating Network Pharmacology and Experimental Validation of Oleanolic Acid Targeting the PPARα-CPT1A Axis to Modulate Lipid Metabolism in Hepatocellular Carcinoma Cells.International journal of molecular sciences · 2026Article
- Fenofibrate as an anti-cancer treatment: an in vitro study on glioblastoma cells at various oxygen levels and on normal astrocytes.Cancer cell international · 2026Article
- The KRT15 and KRT81 complex promotes lenvatinib resistance in thyroid cancer by upregulating DGKB mediated lipid metabolism.Scientific reports · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Multi-omics integration in deciphering non-small cell lung cancer drug resistance: current status, challenges, and future prospects.Hereditas · 2026Review
- Edge-rich Cu-NTheranostics · 2026Article
- Characterization of ANXA1 in chemotherapy resistance of head and neck squamous cell carcinoma: insights from artificial intelligence and integrative bioinformatics analysis.Frontiers in cell and developmental biology · 2026Article
- CDCSI: a machine learning-based interpretable cell death and cellular senescence index for prognosis improvement, immune landscape characterization, and therapeutic response prediction in head and neck squamous cell carcinoma.Frontiers in immunology · 2026Article
- Understanding the Tumor Microenvironment and Therapy Resistance in Head and Neck Squamous Cell Carcinoma.Cells · 2025Review
- Metabolomic and transcriptomic profiling of HNSCC identifies AMIGO2 as a therapeutic target modulating tumor microenvironment.NPJ precision oncology · 2025Article
- Anti-tumor efficacy and Vδ2 T-cell activation via EGFR antibody-drug conjugates featuring novel aminobisphosphonates.Scientific reports · 2025Article
- Mechanisms of Resistance to Chemotherapy in Hypopharyngeal Carcinoma.Biomedicines · 2025Review
- Cetuximab modifies the release and protein content of tumor microvesicles from head and neck squamous cell carcinoma cells: What are the consequences on endothelial cells?Journal of cell communication and signaling · 2025Article
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Authors and funding
30 authors.
Valentin Van den Bossche *Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0001-5443-6641
Julie Vignau *Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.
Engy Vigneron *Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.ORCID http://orcid.org/0009-0006-2769-3857
Isabella RizziPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.
Hannah ZaryouhCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-4567-1399
An WoutersCenter for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium.
Jérôme AmbroiseCentre des Technologies Moléculaires Appliquées (CTMA), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 54, B-1200, Brussels, Belgium.
Steven Van LaereTranslational Cancer Research Unit (TCRU), GZA Ziekenhuizen, Antwerp, Belgium.
Simon BeyaertKing Albert II Cancer Institute, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200, Brussels, Belgium.
Raphaël HelaersLaboratory of Human Molecular Genetics, de Duve Institute, UCLouvain, B-1200, Brussels, Belgium.
Cédric van MarckeKing Albert II Cancer Institute, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0003-3454-0630
Lionel MignionBiomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, UCLouvain, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0002-9426-8600
Elise Y LepicardBiomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, UCLouvain, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0002-9021-2060
Bénédicte F JordanBiomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, UCLouvain, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0002-7126-2206
Céline GuilbaudPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.
Olivier LowyckKing Albert II Cancer Institute, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200, Brussels, Belgium.ORCID http://orcid.org/0009-0007-7320-1005
Hajar DahouPole of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B-1200, Brussels, Belgium.
Antonella MendolaPole of Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B-1200, Brussels, Belgium.
Manon DesgresPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0003-2777-9010
Léo AubertPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0003-1499-0853
Isabelle GerinMetabolic Research Group, de Duve Institute, UCLouvain, B-1200, Brussels, Belgium.
Guido T BommerMetabolic Research Group, de Duve Institute, UCLouvain, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0001-6898-4884
Romain BoidotUnit of Molecular Biology, Department of Biology and Pathology of Tumors, Georges‑François Leclerc Cancer Center‑UNICANCER, 21079, Dijon, France.ORCID http://orcid.org/0000-0001-9956-1737
Perrine VermondenLouvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, Croix du Sud 4-5/L7.07.03, B-1348, Louvain-la-Neuve, Belgium.
Aurélien WarnantLouvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, Croix du Sud 4-5/L7.07.03, B-1348, Louvain-la-Neuve, Belgium.
Yvan LarondelleLouvain Institute of Biomolecular Science and Technology (LIBST), UCLouvain, Croix du Sud 4-5/L7.07.03, B-1348, Louvain-la-Neuve, Belgium.ORCID http://orcid.org/0000-0001-7770-6747
Jean-Pascal MachielsKing Albert II Cancer Institute, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200, Brussels, Belgium.
Olivier FeronPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.ORCID http://orcid.org/0000-0001-5360-0286
Sandra SchmitzKing Albert II Cancer Institute, Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200, Brussels, Belgium.
Cyril CorbetPole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium. cyril.corbet@uclouvain.be.ORCID http://orcid.org/0000-0001-8795-9131
Funding
Fonds De La Recherche Scientifique - FNRS (Belgian National Fund for Scientific Research) Crédit de Recherche J001023
Abstract
Anti-epidermal growth factor receptor (EGFR) therapy (cetuximab) shows a limited clinical benefit for patients with locally advanced or recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), due to the frequent occurrence of secondary resistance mechanisms. Here we report that cetuximab-resistant HNSCC cells display a peroxisome proliferator-activated receptor alpha (PPARα)-mediated lipid metabolism reprogramming, with increased fatty acid uptake and oxidation capacities, while glycolysis is not modified. This metabolic shift makes cetuximab-resistant HNSCC cells particularly sensitive to a pharmacological inhibition of either carnitine palmitoyltransferase 1A (CPT1A) or PPARα in 3D spheroids and tumor xenografts in mice. Importantly, the PPARα-related gene signature, in human clinical datasets, correlates with lower response to anti-EGFR therapy and poor survival in HNSCC patients, thereby validating its clinical relevance. This study points out lipid metabolism rewiring as a non-genetic resistance-causing mechanism in HNSCC that may be therapeutically targeted to overcome acquired resistance to anti-EGFR therapy.
Indexed as
CetuximabDrug Resistance, NeoplasmHead and Neck NeoplasmsLipid MetabolismPPAR alphaSquamous Cell Carcinoma of Head and NeckAnimalsAntineoplastic Agents, ImmunologicalCarnitine O-PalmitoyltransferaseCell Line, TumorErbB ReceptorsFatty AcidsFemaleGene Expression Regulation, NeoplasticGlycolysisHumansAntineoplastic Agents, ImmunologicalCarnitine O-PalmitoyltransferaseCetuximabCPT1A protein, humanEGFR protein, humanErbB ReceptorsFatty AcidsPPAR alphaPPARA protein, human
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