Targeting FGFR in bladder cancer: ready for clinical practice?

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Advances in molecular understanding of bladder urothelial carcinoma (UC) are driving targeted therapy development.
• Next-generation sequencing (NGS) facilitates identification of biomarkers and therapeutic targets in UC.
• Fibroblast growth factor receptor (FGFR) pathway aberrations are implicated in UC tumorigenesis and represent key drug targets.

Purpose of the Study:

• To provide a literature overview of current knowledge on FGFR inhibition in bladder cancer.
• To summarize the efficacy and safety of FGFR inhibitors in advanced or metastatic UC.
• To explore the utility of FGFR aberrations as predictive biomarkers.

Main Methods:

• Literature review of clinical trials and molecular studies on FGFR inhibition in bladder cancer.
• Analysis of data from trials assessing selective and non-selective FGFR inhibitors.
• Evaluation of methods for detecting FGFR aberrations, including NGS of tumor tissue and liquid biopsies (ctDNA, cfDNA).

Main Results:

• Selective 'pan'-FGFR inhibitors demonstrate favorable response rates and manageable toxicity compared to non-selective inhibitors.
• FGFR aberrations can be effectively screened using NGS in tumor tissue, ctDNA, or cfDNA.
• Early clinical trials indicate promising efficacy for FGFR-targeted therapies in advanced UC.

Conclusions:

• Targeting FGFR represents a promising therapeutic strategy for advanced or metastatic UC.
• FGFR aberrations detected in liquid biopsies (ctDNA, cfDNA) show potential as non-invasive predictive biomarkers.
• Further validation in Phase III trials is necessary to confirm these findings.