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Bladder cancer

iCAFs control chemoresistance

Nature Reviews Urology volume 22, page 495 (2025)Cite this article

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Distinct populations of cancer-associated fibroblasts (CAFs) that influence therapy response have been discovered in bladder cancer. Inflammatory CAFs (iCAFs) support the expansion of cancer stem cells, driving chemoresistance and providing potential therapeutic targets.

Analysis of matched prechemotherapy and postchemotherapy tumour samples from patients with chemoresistant bladder cancer revealed a significantly enriched fibroblast gene signature in postchemotherapy samples (P < 0.0001). Specifically, notable upregulation of COL3A1, IL6 and PDGFRB was observed. However, no increase in the classical myofibroblastic CAF (myCAF) marker ACTA2 was found. Multiplex immunohistochemistry costaining for αSMA with PDGFRβ, collagen III and IL-6 in human bladder cancer tissue sections showed the existence of two CAF subpopulations: αSMA+PDGFRβ+ and αSMA−PDGFRβ+. Most CAFs in both subpopulations also expressed IL-6.

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  1. Nature Reviews Urology http://www.nature.com/nrurol/

    Louise Lloyd

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  1. Louise Lloyd
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Correspondence to Louise Lloyd.

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Lloyd, L. iCAFs control chemoresistance. Nat Rev Urol 22, 495 (2025). https://doi.org/10.1038/s41585-025-01068-w

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