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Nectin-4在癌症治疗中的前景:应用与价值

Therapeutic prospects of nectin-4 in cancer: applications and value.

作者信息

Li Kaiyue, Zhou Yujing, Zang Maolin, Jin Xin, Li Xin

机构信息

Department of Nuclear Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

出版信息

Front Oncol. 2024 Mar 28;14:1354543. doi: 10.3389/fonc.2024.1354543. eCollection 2024.

Abstract

Nectin-4 is a Ca-independent immunoglobulin-like protein that exhibits significantly elevated expression in malignant tumors while maintaining extremely low levels in healthy adult tissues. In recent years, overexpression of Nectin-4 has been implicated in tumor occurrence and development of various cancers, including breast cancer, urothelial cancer, and lung cancer. In 2019, the Food and Drug Administration approved enfortumab vedotin, the first antibody-drug conjugate targeting Nectin-4, for the treatment of urothelial carcinoma. This has emphasized the value of Nectin-4 in tumor targeted therapy and promoted the implementation of more clinical trials of enfortumab vedotin. In addition, many new drugs targeting Nectin-4 for the treatment of malignant tumors have entered clinical trials, with the aim of exploring potential new indications. However, the exact mechanisms by which Nectin-4 affects tumorigenesis and progression are still unclear, and the emergence of drug resistance and treatment-related adverse reactions poses challenges. This article reviews the diagnostic potential, prognostic significance, and molecular role of Nectin-4 in tumors, with a focus on clinical trials in the field of Nectin-4-related tumor treatment and the development of new drugs targeting Nectin-4.

摘要

NECTIN-4是一种不依赖钙的免疫球蛋白样蛋白,在恶性肿瘤中表达显著升高,而在健康成人组织中维持极低水平。近年来,NECTIN-4的过表达与包括乳腺癌、尿路上皮癌和肺癌在内的多种癌症的肿瘤发生和发展有关。2019年,美国食品药品监督管理局批准了首款靶向NECTIN-4的抗体药物偶联物安维汀(enfortumab vedotin)用于治疗尿路上皮癌。这凸显了NECTIN-4在肿瘤靶向治疗中的价值,并推动了更多安维汀临床试验的开展。此外,许多针对NECTIN-4治疗恶性肿瘤的新药已进入临床试验阶段,旨在探索潜在的新适应症。然而,NECTIN-4影响肿瘤发生和进展的确切机制仍不清楚,耐药性的出现和治疗相关不良反应带来了挑战。本文综述了NECTIN-4在肿瘤中的诊断潜力、预后意义及分子作用,重点关注NECTIN-4相关肿瘤治疗领域的临床试验以及靶向NECTIN-4新药的研发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a709/11007101/080b8e98eaf5/fonc-14-1354543-g001.jpg

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