Nectin-4, Bladder Cancer, and Nuclear Medicine: A Theranostic Frontier.

IF 5.9 2区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
Joseph Kabunda, Honest Ndlovu, Karishma Singh, Sandile Sibiya, Sipho Mdanda, Kamo Ramonaheng, Akram Al-Ibraheem, Ken Herrmann, Kgomotso Mokoala, Mike Sathekge
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Abstract

Bladder cancer is among the top ten most common cancers globally, with advanced or metastatic disease associated with dismal survival outcomes. Current diagnostic imaging and therapies have significant limitations, highlighting the urgent need for novel theranostic targets. Nectin-4, a cell adhesion molecule frequently overexpressed in bladder cancer, especially urothelial carcinoma (∼60%-87% of tumors), has emerged as a promising biomarker and therapeutic target. This review critically evaluates the role of Nectin-4 in bladder cancer and explores its exciting potential in nuclear medicine for combined molecular imaging and targeted radionuclide therapy-embracing the "theranostic" paradigm. Nectin-4 is abundantly and selectively expressed in most urothelial carcinomas, correlating with advanced disease and poorer prognosis. Clinically validated by the FDA-approved antibody-drug conjugate enfortumab vedotin, Nectin-4 targeting achieves objective response rates around 40%-50% and significantly improves survival in refractory advanced urothelial carcinoma. Recent clinical advances in Nectin-4-targeted PET imaging (such as 68Ga-labeled agents) have demonstrated excellent tumor localization and specificity, enabling precise patient selection for targeted therapies. Additionally, emerging radionuclide therapeutics (eg, 225Ac- and 177Lu-based agents) show promising preclinical and early clinical efficacy, robust tumor targeting, and favorable safety profiles. Targeting Nectin-4 represents a new frontier in the management of bladder cancer, bridging the gap between precise molecular diagnostics and personalized targeted radionuclide therapy. Ongoing clinical trials and translational research are rapidly advancing this promising theranostic strategy towards routine clinical application, with significant potential to enhance patient selection, treatment monitoring, and ultimately, clinical outcomes.

Nectin-4,膀胱癌和核医学:治疗前沿。
膀胱癌是全球十大最常见的癌症之一,晚期或转移性疾病与惨淡的生存结果相关。目前的诊断成像和治疗有明显的局限性,突出了迫切需要新的治疗靶点。Nectin-4是一种在膀胱癌,特别是尿路上皮癌(约60%-87%的肿瘤)中经常过表达的细胞粘附分子,已成为一种有前途的生物标志物和治疗靶点。这篇综述批判性地评估了Nectin-4在膀胱癌中的作用,并探讨了其在核医学中结合分子成像和靶向放射性核素治疗的令人兴奋的潜力-拥抱“治疗”范式。Nectin-4在大多数尿路上皮癌中大量和选择性表达,与晚期疾病和较差预后相关。经fda批准的抗体-药物偶联物enfortumab vedotin临床验证,Nectin-4靶向治疗难治性晚期尿路上皮癌的客观缓解率约为40%-50%,显著提高生存率。最近在nectin -4靶向PET成像(如68ga标记剂)方面的临床进展已经证明了出色的肿瘤定位和特异性,可以精确地选择患者进行靶向治疗。此外,新兴的放射性核素疗法(例如,基于225Ac和177lu的药物)显示出有希望的临床前和早期临床疗效,强大的肿瘤靶向性和良好的安全性。靶向Nectin-4代表了膀胱癌治疗的新前沿,弥合了精确分子诊断和个性化靶向放射性核素治疗之间的差距。正在进行的临床试验和转化研究正迅速将这种有前景的治疗策略推向常规临床应用,在加强患者选择、治疗监测以及最终的临床结果方面具有巨大的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Seminars in nuclear medicine
Seminars in nuclear medicine 医学-核医学
CiteScore
9.80
自引率
6.10%
发文量
86
审稿时长
14 days
期刊介绍: Seminars in Nuclear Medicine is the leading review journal in nuclear medicine. Each issue brings you expert reviews and commentary on a single topic as selected by the Editors. The journal contains extensive coverage of the field of nuclear medicine, including PET, SPECT, and other molecular imaging studies, and related imaging studies. Full-color illustrations are used throughout to highlight important findings. Seminars is included in PubMed/Medline, Thomson/ISI, and other major scientific indexes.
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