Recent advances in bladder cancer stem cells (BCSCs): A descriptive review of emerging therapeutic targets

Bladder cancer (BC) is the most common malignancy of the urinary system, characterized by high recurrence due to limited specificity and efficacy of current therapies. Bladder cancer stem cells (BCSCs), a distinct subpopulation within BC, exhibit self-renewal, tumorigenicity, and resistance to conventional treatments, playing a critical role in BC initiation, progression, metastasis, and recurrence. This study reviews the origins, biomarkers, and therapeutic potential of BCSCs, emphasizing emerging strategies targeting these cells. BCSCs can arise from urothelial stem cells or differentiated cells, with markers such as CD44, EZH2, ALDH1A1, and SOX2 enabling their identification. Aberrant activation of multiple signaling pathways, including Hedgehog, Notch, Wnt, PI3K/Akt, STAT3, and Hippo-YAP, drives BCSC function and therapy resistance. Targeting these pathways and markers offers promising therapeutic approaches to enhance efficacy and reduce recurrence. Understanding BCSC biology provides insights into improving treatment outcomes and advancing BC management strategies.