Nadeem Abdullah, Qamar Khulud, Bilal Wajeeha, Vohra Laiba Imran, Ahsan Areeba, Tariq Rabeea
Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Department of Medicine, Ziauddin University, Karachi, Pakistan.
Front Urol. 2023 Sep 15;3:1206398. doi: 10.3389/fruro.2023.1206398. eCollection 2023.
Muscle-invasive bladder tumors pose a grave mortality risk due to their propensity for distant metastases. The therapeutic spectrum for such tumors encompasses surgery, chemotherapy, and radiation, tailored to the cancer's severity. In the context of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC), a novel treatment has emerged as a beacon of hope. Nadofaragene firadenovec, a pioneering gene therapy, has gained worldwide approval for combating this condition, marking a watershed moment in bladder cancer therapy. Nadofaragene firadenovec is ingeniously designed to address high-risk BCG-unresponsive NMIBC, particularly carcinoma (CIS) with or without papillary tumors, in adult patients. Rooted in a vector DNA, this therapy encodes interferon (IFN)-2b, which imparts urothelial cells with the ability to generate IFN-2b. The resulting cascade of events triggers a multifaceted assault on cancer, characterized by its immunostimulatory, antiangiogenic, and apoptotic effects. The therapeutic efficacy of nadofaragene firadenovec rests on its capacity to exploit the transformed urothelial cells to deliver these targeted anticancer activities. The evolutionary trajectory of nadofaragene firadenovec culminated in its monumental approval in December 2022 by the United States, signifying a pivotal juncture in the field. Notably, a segment of patients, approximately 30%, prove refractory to BCG treatment. For these individuals, alternative therapeutic avenues are imperative. Presently, the landscape for patients with non-muscle invasive bladder cancer lacks a definitive, enduring solution. Against this backdrop, the introduction of nadofaragene firadenovec heralds a momentous stride toward the global availability of an authorized therapeutic intervention.
肌肉浸润性膀胱肿瘤因其易于发生远处转移而带来严重的死亡风险。此类肿瘤的治疗方法包括手术、化疗和放疗，具体治疗方案会根据癌症的严重程度进行调整。在高危卡介苗（BCG）无反应的非肌肉浸润性膀胱癌（NMIBC）的背景下，一种新的治疗方法成为了希望之光。纳多福韦基因腺病毒载体（Nadofaragene firadenovec），一种开创性的基因疗法，已在全球范围内获得治疗这种疾病的批准，标志着膀胱癌治疗的一个分水岭。纳多福韦基因腺病毒载体被巧妙设计用于治疗成年患者的高危BCG无反应性NMIBC，特别是伴有或不伴有乳头状肿瘤的原位癌（CIS）。这种疗法基于载体DNA，编码干扰素（IFN）-2b，使尿路上皮细胞能够产生IFN-2b。由此引发的一系列事件触发了对癌症的多方面攻击，其特点是具有免疫刺激、抗血管生成和凋亡作用。纳多福韦基因腺病毒载体的治疗效果取决于其利用转化的尿路上皮细胞来传递这些靶向抗癌活性的能力。纳多福韦基因腺病毒载体的发展历程在2022年12月获得美国的重大批准时达到顶峰，这标志着该领域的一个关键转折点。值得注意的是，约30%的患者对BCG治疗无效。对于这些患者来说，必须有其他治疗途径。目前，非肌肉浸润性膀胱癌患者的治疗领域缺乏一种确定的、持久的解决方案。在此背景下，纳多福韦基因腺病毒载体的引入预示着朝着全球可获得一种经批准的治疗干预措施迈出了重要一步。
