Gene-mediated therapy for BCG-unresponsive nonmuscle-invasive bladder cancer: mechanisms, clinical evidence, and...

Area of Science:

• Oncology
• Gene Therapy
• Urology

Background:

• Nonmuscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG) treatment presents a significant therapeutic challenge.
• Radical cystectomy is often considered for high-risk NMIBC, but bladder-sparing options are needed for eligible patients.
• Gene therapy offers a novel strategy to address this unmet need in BCG-unresponsive NMIBC.

Purpose of the Study:

• To review recent advancements in gene-mediated therapies for patients with BCG-unresponsive nonmuscle-invasive bladder cancer (NMIBC).
• To highlight the potential of gene therapy as a bladder-sparing alternative to radical cystectomy.

Main Methods:

• Review of current literature on gene therapy applications in NMIBC.
• Analysis of emerging gene delivery platforms and vector engineering.
• Evaluation of combination strategies with immunotherapy.

Main Results:

• The bladder's anatomy facilitates efficient intravesical gene delivery.
• Adenoviral vectors, including FDA-approved nadofaragene firadenovec (Adstiladrin) and oncolytic adenoviruses (cretostimogene, CG0070), show promise.
• Combination regimens with immune checkpoint inhibitors enhance gene therapy durability.
• Urinary and plasma tumor DNA are emerging as predictive biomarkers for patient selection and monitoring.

Conclusions:

• Gene-mediated therapy is evolving as a key component in managing NMIBC.
• Expanding indications and potent combination therapies are expected to improve bladder preservation rates.
• Gene therapy holds significant potential for enhancing long-term outcomes in NMIBC patients.