The current status of gene therapy in bladder cancer

Gene therapy aims to alter the biological properties of cells through the therapeutic delivery of nucleotides to treat a disease. Although originally developed to treat genetic disorders, the majority of gene therapy development today is for the treatment of cancer, including bladder cancer.

Following a brief history and a discussion of the mechanisms of gene therapy, we will focus on the current and future gene therapy strategies for bladder cancer. We will review the most consequential clinical trials published in the field.

Recent transformative breakthroughs in bladder cancer research have deeply characterized the major epigenetic and genetic alterations of bladder cancer and have radically transformed our view of tumor biology and generated new hypotheses for therapy. These advances provided the opportunity to begin to optimize strategies for effective gene therapy for bladder cancer. Clinical trials have shown promising results, especially in BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC), where effective second-line therapy remains an unmet need for patients facing cystectomy. Efforts are underway to develop effective combination strategies targeting resistance mechanisms to gene therapy for NMIBC.