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.