Advances in FGFR Inhibition for Bladder Cancer: A Review of Molecular Targets and Therapeutic Progress

Abstract

Bladder cancer (BC) ranks among the most prevalent urological malignancies globally, presenting with a wide spectrum of clinical behavior from non-muscle-invasive to deeply invasive and metastatic forms. Despite progress in surgical interventions, chemotherapy, and immunotherapy, challenges such as high recurrence rates and therapeutic resistance persist, particularly in advanced disease stages. This review provides an indepth analysis of current understanding of BC, including its epidemiology, classification, diagnostic tools, and standard treatment approaches. Special attention is given to the fibroblast growth factor receptor (FGFR) signaling pathway, a key molecular driver increasingly recognized for its role in tumor progression. Alterations in FGFR, especially FGFR3 mutations and gene fusions, are frequently observed in non-muscle-invasive and luminal subtypes and carry important prognostic and therapeutic implications. The recent clinical approval of FGFR inhibitors, such as erdafitinib, marks a promising advancement in precision oncology, offering targeted options for patients with FGFR-altered tumors. Ongoing clinical trials are exploring combinatorial therapies and resistance mechanisms to further enhance outcomes. A more thorough knowledge of FGFR-driven oncogenesis is essential for developing more refined, personalized treatment strategies. This review underscores the transformative potential of molecular profiling and FGFR-targeted therapies in the evolving management of bladder cancer.