Metabolic Reprogramming in Bladder Cancer: Molecular Drivers, Immune Regulation and Therapeutic Opportunities.
- 1Department of Urology, Affiliated Hospital of Chifeng University, Chifeng 024005, China.
- 2General Office, Affiliated Hospital of Chifeng University, Chifeng 024005, China.
- 3Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Abstract
Metabolic reprogramming is increasingly recognised as a central determinant of bladder cancer heterogeneity, immune regulation and treatment response. This review integrates genetic, epigenetic, microenvironmental and therapeutic evidence to explain how bladder cancer redistributes carbon and nitrogen across glycolysis, lipid synthesis and oxidation, amino-acid metabolism and mitochondrial respiration. Alterations in FGFR3, PIK3CA, MYC, TP53/RB1 and KDM6A establish distinct, context-dependent metabolic dependencies, while hypoxia, extracellular-matrix mechanics and treatment selection reinforce metabolic plasticity. These programmes influence not only energy production and biosynthesis but also ferroptosis, genome stability and chromatin or RNA regulation. Lactate, adenosine, kynurenine and asparagine further connect tumour metabolism to regulatory T cells, myeloid cells, innate immune sensing and CD8-positive T cell function, thereby shaping resistance to chemotherapy and immune-checkpoint blockade. Therapeutic opportunities include targeting glycolysis, fatty-acid and cholesterol metabolism, glutamine and proline metabolism, arginine auxotrophy and metabolite-mediated immune suppression. However, pathway redundancy, cellular heterogeneity and shared metabolic requirements between tumour and immune cells constrain unselected treatment. Urine, tissue, blood and imaging metabolomics offer complementary routes to diagnosis, prognostication and real-time response monitoring, but require harmonised sampling, functional flux measurements and prospective validation. A clinically useful strategy will therefore depend on defining metabolic vulnerabilities by genotype, cell type, spatial context and treatment stage, and on pairing pharmacodynamic biomarkers with rational combinations and local delivery where appropriate.
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BibTeX
@article{li2026metabolic,
title = {{Metabolic Reprogramming in Bladder Cancer: Molecular Drivers, Immune Regulation and Therapeutic Opportunities.}},
author = {Shaolin Li and Minghui Li and Yinglang Zhang and Jie Pu and Jiaao Sun and Chunsheng Li and Changgang Guo},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18193202},
url = {https://europepmc.org/article/MED/42882896},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metabolic Reprogramming in Bladder Cancer: Molecular Drivers, Immune Regulation and Therapeutic Opportunities.
AU - Shaolin Li
AU - Minghui Li
AU - Yinglang Zhang
AU - Jie Pu
AU - Jiaao Sun
AU - Chunsheng Li
AU - Changgang Guo
PY - 2026
DA - 2026/10/03
JO - Cancers
DO - 10.3390/cancers18193202
UR - https://europepmc.org/article/MED/42882896
AB - Metabolic reprogramming is increasingly recognised as a central determinant of bladder cancer heterogeneity, immune regulation and treatment response. This review integrates genetic, epigenetic, microenvironmental and therapeutic evidence to explain how bladder cancer redistributes carbon and nitrogen across glycolysis, lipid synthesis and oxidation, amino-acid metabolism and mitochondrial respiration. Alterations in FGFR3, PIK3CA, MYC, TP53/RB1 and KDM6A establish distinct, context-dependent metabolic dependencies, while hypoxia, extracellular-matrix mechanics and treatment selection reinforce metabolic plasticity. These programmes influence not only energy production and biosynthesis but also ferroptosis, genome stability and chromatin or RNA regulation. Lactate, adenosine, kynurenine and asparagine further connect tumour metabolism to regulatory T cells, myeloid cells, innate immune sensing and CD8-positive T cell function, thereby shaping resistance to chemotherapy and immune-checkpoint blockade. Therapeutic opportunities include targeting glycolysis, fatty-acid and cholesterol metabolism, glutamine and proline metabolism, arginine auxotrophy and metabolite-mediated immune suppression. However, pathway redundancy, cellular heterogeneity and shared metabolic requirements between tumour and immune cells constrain unselected treatment. Urine, tissue, blood and imaging metabolomics offer complementary routes to diagnosis, prognostication and real-time response monitoring, but require harmonised sampling, functional flux measurements and prospective validation. A clinically useful strategy will therefore depend on defining metabolic vulnerabilities by genotype, cell type, spatial context and treatment stage, and on pairing pharmacodynamic biomarkers with rational combinations and local delivery where appropriate.
SN - 2072-6694
ER -