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Review Open Access

Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review)

  • Authors:
    • Li Yan
    • Pengxiao Su
    • Xiaoke Sun
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China, Department of Urology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, P.R. China
    Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 293
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    Published online on: August 19, 2025
       https://doi.org/10.3892/mmr.2025.13658
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Abstract

Urothelial carcinoma (UC) presents considerable treatment challenges, primarily due to the high rates of therapeutic resistance observed in affected patients. Currently, therapeutic strategies often fail to yield satisfactory outcomes; therefore, there is a need for innovative treatment approaches. The tumor microenvironment (TME) serves a key role in driving treatment resistance in UC, revealing that components such as cancer‑associated fibroblasts, tumor‑associated macrophages and the extracellular matrix contribute to tumor survival and evasion of therapy. Understanding the mechanisms through which the TME influences treatment resistance is key for developing effective countermeasures. Targeting the TME may be an effective therapeutic strategy, as this approach may increase the efficacy of existing treatments and overcome barriers to response. The present review aims to summarize current knowledge regarding the role of the TME in UC treatment resistance, discuss potential strategies for targeting the TME and highlight future research directions. The translation of insights from studies on the TME into therapeutic strategies may improve clinical outcomes for patients suffering from this challenging malignancy.
View Figures

Figure 1

Composition of the tumor
microenvironment in urothelial carcinoma. This image was drawn
using Figdraw (www.figdraw.com; ID: UORAS20309). CAFs,
cancer-associated fibroblasts; ECM, extracellular matrix.

Figure 2

Diagram presenting the role of the
tumor microenvironment of UC on therapeutic resistance. This image
was drawn using Figdraw (www.figdraw.com; ID: UIAIT9e999). UC, urothelial
carcinoma; TAMs, tumor-associated macrophages; NKs, natural
killers; MDSCs, myeloid-derived suppressor cells; Treg, regulatory
T cell; PD-L1, programmed death-ligand 1; PD-1, programmed death 1;
CAFs, cancer-associated fibroblasts; ECM, extracellular matrix.
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Copy and paste a formatted citation
Spandidos Publications style
Yan L, Su P and Sun X: Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review). Mol Med Rep 32: 293, 2025.
APA
Yan, L., Su, P., & Sun, X. (2025). Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review). Molecular Medicine Reports, 32, 293. https://doi.org/10.3892/mmr.2025.13658
MLA
Yan, L., Su, P., Sun, X."Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review)". Molecular Medicine Reports 32.5 (2025): 293.
Chicago
Yan, L., Su, P., Sun, X."Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review)". Molecular Medicine Reports 32, no. 5 (2025): 293. https://doi.org/10.3892/mmr.2025.13658
Copy and paste a formatted citation
x
Spandidos Publications style
Yan L, Su P and Sun X: Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review). Mol Med Rep 32: 293, 2025.
APA
Yan, L., Su, P., & Sun, X. (2025). Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review). Molecular Medicine Reports, 32, 293. https://doi.org/10.3892/mmr.2025.13658
MLA
Yan, L., Su, P., Sun, X."Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review)". Molecular Medicine Reports 32.5 (2025): 293.
Chicago
Yan, L., Su, P., Sun, X."Role of the tumor microenvironment in promoting treatment resistance in urothelial carcinoma (Review)". Molecular Medicine Reports 32, no. 5 (2025): 293. https://doi.org/10.3892/mmr.2025.13658
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