Integrating gene therapy into the treatment paradigm for non-muscle invasive bladder cancer

Area of Science:

• Oncology
• Gene Therapy
• Urothelial Carcinomas

Background:

• Non-muscle invasive bladder cancer (NMIBC) constitutes approximately 75% of diagnoses.
• Drug development for NMIBC has historically faced challenges, with limited options to overcome treatment resistance and prevent recurrence.
• Gene therapy is emerging as a novel and promising therapeutic strategy for NMIBC management.

Purpose of the Study:

• To review the clinical applications of gene therapy in NMIBC.
• To discuss recent clinical trials of adenoviral vector-based gene therapies, including nadofaragene firadenovec and cretostimogene grenadenorepvec.
• To explore strategies for enhancing the efficacy and durability of gene therapies for NMIBC.

Main Methods:

• Review of clinical trials and literature on gene therapy for NMIBC.
• Summary of recent advancements in adenoviral vector-based treatments.
• Analysis of ongoing research investigating combination therapies and novel agents.

Main Results:

• Nadofaragene firadenovec received FDA approval in December 2022.
• Cretostimogene grenadenorepvec has received FDA Fast Track and Breakthrough Therapy Designations.
• Gene therapies show potential to overcome resistance mechanisms and may be effective in combination with other agents.

Conclusions:

• Gene therapy represents a significant advancement in NMIBC treatment, offering a new approach to overcome drug resistance.
• Ongoing research focuses on improving the efficacy and durability of gene therapies, with expanding interest in various patient populations.
• Critical assessment of trial designs is necessary for comparing different gene therapy agents and informing future clinical practice.