The future of bladder cancer therapy: Optimizing the inhibition of the fibroblast growth factor receptor

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Metastatic bladder cancer (BC) treatment options have been limited, with platinum-based chemotherapy as the standard for decades.
• Recent approvals of immune checkpoint inhibitors (ICIs) offer new therapeutic avenues for metastatic BC.
• The Cancer Genome Atlas identified fibroblast growth factor (FGF) axis alterations in approximately 15% of muscle-invasive bladder cancer (MIBC) cases.

Purpose of the Study:

• To review the current knowledge of FGF signaling pathways in bladder cancer.
• To summarize the prognosis associated with FGFR mutations in BC.
• To discuss the efficacy, safety, and resistance mechanisms of FGFR inhibitors in metastatic BC.

Main Methods:

• Literature review of studies published over the last decade focusing on FGF signaling and FGFR inhibitors in bladder cancer.
• Analysis of efficacy and safety data for FGFR inhibitors in selected populations of metastatic BC with FGFR aberrations.
• Exploration of current strategies for managing resistance to anti-FGFR agents.

Main Results:

• Fibroblast growth factor receptor (FGFR) inhibitors, such as erdafitinib, have emerged as a targeted therapy for metastatic BC patients with FGFR genomic aberrations.
• FGFR inhibitors demonstrate efficacy in patients who have progressed on platinum-based chemotherapy.
• Understanding mechanism-based toxicities and developing biomarkers are crucial for optimizing FGFR inhibitor therapy.

Conclusions:

• Targeted therapies, particularly FGFR inhibitors, represent a significant advancement in treating metastatic bladder cancer with specific molecular alterations.
• Further research into resistance mechanisms and biomarker development is essential for personalized treatment approaches.
• The therapeutic landscape for metastatic BC is shifting towards individualized strategies based on molecular profiling.