ArticleBritish journal of cancer2026
Pan-cancer analysis of pyrimidine metabolism reveals signaling pathways connections with chemoresistance role.
Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- An immunometabolic prodrug strategy overcomes DHODH inhibitor resistance in refractory melanoma.Journal of experimental & clinical cancer research : CR · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
backgroundDeregulated pyrimidine metabolism (PyMet) contributes to various tumorigenic features of cancer, including chemoresistance and epithelial-to-mesenchymal transition. However, cancer often encompasses complex signalling and metabolic pathway cascades for its progression and understanding of these molecular regulatory processes in PyMet is quite limited.
methodsA comprehensive pan-cancer analysis of around 10,000 gene expression profiles of 32 cancer types was employed using a pathway-based approach utilising gene-sets of signalling and metabolic pathways. The findings were validated using in vitro inhibitor treatments, genetic perturbations and mouse-derived lung tumour organoids.
resultsPan-cancer analysis identified several top connections with PyMet, including TERT, MTOR, DAX1, HOXA1, TP53 and TNC, implying an interdependency of regulations, which in turn was linked to the chemoresistance mechanisms. Further, these PyMet-signalling interactions were validated in vitro by inhibiting thymidylate synthase (TS) activity using knockdown approach and by brequinar (BRQ), a DHODH inhibitor. Strikingly, the BRQ treatment profile showed a strong inverse association pattern with doxorubicin chemoresistance in multiple cancer types. Indeed, BRQ synergistically sensitises cells to doxorubicin in both lung cancer cell lines and mouse-derived Kras
conclusionsThe study highlights the PyMet-pathway interactions and its role in chemoresistance, providing a strategy for targeting PyMet in cancer.
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