Metabolic Reprogramming in the Bladder Cancer Microenvironment: Bridging Fundamental Research and Therapeutic Avenues for Cancer-Associated Fibroblasts.

Bladder cancer (BC) is one of the most common malignancies of the urinary tract, characterized by high recurrence rates and, in advanced stages, resistance to therapy and poor prognosis. Cancer and stromal cells of the BC microenvironment often undergo metabolic reprogramming to meet the demands of rapid growth and survival. These metabolic changes enable cancer cells to thrive under stressful conditions, support drug resistance, and contribute to tumor progression. Bladder cancer-associated fibroblasts (BCAFs) are key components of the tumor microenvironment and play a significant role in BC development and progression. Besides influencing cancer cell metabolism by altering nutrient availability and facilitating metabolic crosstalk, they secrete growth factors, cytokines, and extracellular matrix proteins that support tumor growth, modulate immune responses, and promote invasion, metastasis and resistance to therapy. In this review, we compiled current knowledge on the origin, development, function, and potential therapeutic applications of BCFAs. Particular emphasis was placed on the metabolic interplay between BCAFs and BC cells, as well as their mutual modulation.