[Personalised medicine in urothelial bladder cancer]

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• Urothelial bladder cancer treatment outcomes, particularly for metastatic disease, have seen limited improvement over decades.
• Recent advances in high-throughput analyses and understanding tumor immune surveillance have reshaped insights into bladder cancer biology.

Purpose of the Study:

• To explore the potential of personalized therapeutic approaches for urothelial bladder cancer based on genetic mutations and molecular subtypes.
• To discuss the role of immune checkpoint inhibitors and the need for predictive biomarkers in bladder cancer treatment.

Main Methods:

• Review of current understanding of urothelial bladder cancer biology, including genetic alterations and molecular subtypes.
• Analysis of emerging therapeutic strategies such as targeted therapies (FGFR, PARP inhibitors) and immune checkpoint inhibitors.
• Discussion of challenges in clinical implementation, including tumor heterogeneity and the need for prospective evaluation of biomarkers.

Main Results:

• Genetic mutations and molecular subtypes offer potential for tailor-made therapies, with DNA repair pathway alterations predicting chemotherapy response.
• Targeted therapies (FGFR, PARP inhibitors) are under clinical investigation.
• Immune checkpoint inhibitors represent a significant advancement, though response rates are limited (25%), underscoring the need for predictive biomarkers.

Conclusions:

• Personalized medicine approaches for urothelial bladder cancer are advancing, driven by molecular insights.
• Prospective evaluation of molecular subtypes and biomarkers is crucial for clinical integration.
• Addressing tumor heterogeneity and improving response rates to immunotherapy remain key challenges.