2. Academic Validation
  3. FGFR3 oncogenic activation drives oxidative metabolic reprogramming in bladder cancer: a systems metabolomics approach

FGFR3 oncogenic activation drives oxidative metabolic reprogramming in bladder cancer: a systems metabolomics approach

  • Commun Biol. 2026 May 23. doi: 10.1038/s42003-026-10356-z.
Giacomo Ducci # 1 2,  Giorgia Ciufolini # 3,  Gloria Campioni 1 2,  Valentina Pasquale 1 2,  Giulia Gigliotti 1 2,  Simone Ponzetto 1 2,  Daniele Benedetti 1 2,  Bruno Giovanni Galuzzi 4,  Deborah D'Aliberti 5,  Silvia Spinelli 5,  Vrunda Satasiya 6 7,  Elisa Ventura 6 8,  Chiara Raggi 9,  Riccardo Vago 8 10,  Marcella Bonanomi 2 11,  Daniela Gaglio 2 11,  Antonio Giordano 6 7,  Andrea Morrione 6,  Chiara Damiani 1 2,  Rocco Piazza 5,  Daniel Oscar Cicero 3,  Marco Vanoni 12 13,  Greta Petrella 14,  Elena Sacco 15 16
Affiliations

Affiliations

  • 1 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
  • 2 SYSBIO-ISBE-IT-Candidate National Node of Italy for ISBE, Research Infrastructure for Systems Biology Europe, Milan, Italy.
  • 3 Department of Chemical Science and Technology, University of Rome "Tor Vergata", Rome, Italy.
  • 4 Institute of Molecular Bioimaging and Physiology, National Research Council, Segrate, Italy.
  • 5 Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
  • 6 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
  • 7 Department of Medical Biotechnologies, University of Siena, Siena, Italy.
  • 8 Vita-Salute San Raffaele University, Milan, Italy.
  • 9 Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
  • 10 Urological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milan, Italy.
  • 11 Institute of Bioimaging and Complex Biological Systems, National Research Council, Segrate, Italy.
  • 12 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy. [email protected].
  • 13 SYSBIO-ISBE-IT-Candidate National Node of Italy for ISBE, Research Infrastructure for Systems Biology Europe, Milan, Italy. [email protected].
  • 14 Department of Chemical Science and Technology, University of Rome "Tor Vergata", Rome, Italy. [email protected].
  • 15 Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy. [email protected].
  • 16 SYSBIO-ISBE-IT-Candidate National Node of Italy for ISBE, Research Infrastructure for Systems Biology Europe, Milan, Italy. [email protected].
  • # Contributed equally.
PMID: 42177363 DOI: 10.1038/s42003-026-10356-z
Abstract

Bladder Cancer is one of the most common malignancies worldwide, impacting public health systems due to its high rate of recurrence. Metabolic alterations enable the identification of novel, needed prognostic markers and therapeutic vulnerabilities for precision oncology. Here, we use a systems metabolomics approach that integrates metabolic functional data with multi-omics, transcriptomics and metabolomics, through biostatistics and mathematical modelling to characterise metabolic rearrangements associated with FGFR3 oncogenic activation, one of the most frequent lesions in bladder Cancer. The analyses conducted on a panel of five human bladder Cancer cell lines reveal a significant correlation between FGFR3 alterations and the acquisition of a predominantly oxidative, poorly migratory phenotype, regardless of tumour progression. These preclinical results, validated through FGFR3 and Oxidative Phosphorylation pharmacological inhibition, and computational analysis on bladder Cancer cell line and patient publicly available datasets, support the therapeutic potential of targeting oxidative metabolism in FGFR3-altered tumours, including more aggressive subtypes.

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