Tholomier Côme, Martini Alberto, Mokkapati Sharada, Dinney Colin P
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Urology,Division of Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Expert Rev Anticancer Ther. 2023 May;23(5):531-543. doi: 10.1080/14737140.2023.2203385. Epub 2023 Apr 25.
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.
基因治疗旨在通过治疗性递送核苷酸来改变细胞的生物学特性，以治疗疾病。尽管基因治疗最初是为治疗遗传疾病而开发的，但如今大多数基因治疗的研发是针对癌症，包括膀胱癌。
在简要介绍基因治疗的历史并讨论其机制之后，我们将重点关注当前和未来的膀胱癌基因治疗策略。我们将回顾该领域发表的最重要的临床试验。
膀胱癌研究中最近的变革性突破深入描绘了膀胱癌主要的表观遗传和基因改变，从根本上改变了我们对肿瘤生物学的看法，并产生了新的治疗假设。这些进展为开始优化膀胱癌有效基因治疗策略提供了机会。临床试验已显示出有前景的结果，特别是在卡介苗无反应的非肌层浸润性膀胱癌（NMIBC）中，对于面临膀胱切除术的患者来说，有效的二线治疗仍然是未满足的需求。目前正在努力开发针对NMIBC基因治疗耐药机制的有效联合策略。
