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从成纤维细胞活化蛋白解读肿瘤:最新诊断与治疗前景综述

Decoding tumors from fibroblast activation protein: A review of the latest diagnostic and therapeutic prospects.

作者信息

Wang Qi, Song Chang, Zhao Chunyan, Wei Xiuyun, Li Deli, Wu Qinting, Li Jing, Yang Xiaomei

机构信息

School of Basic Medical Science, Guangxi Medical University, Nanning, Guangxi 530021, PR China.

School of oncology, Guangxi Medical University, Nanning, Guangxi 530021, PR China.

出版信息

Int J Biol Macromol. 2025 Jul;318(Pt 2):145006. doi: 10.1016/j.ijbiomac.2025.145006. Epub 2025 Jun 6.

Abstract

Fibroblast activation protein (FAP), as a molecule closely associated with the tumor microenvironment (TME), has garnered widespread attention in recent years. FAP is a type II transmembrane serine protease primarily expressed in cancer-associated fibroblasts (CAFs), and it plays a significant role in tumor growth, invasion, metastasis, and immune evasion processes. FAP is highly expressed in over 90 % of epithelial cancers, which makes it a satisfactory diagnostic marker on account of its exceptional sensitivity and specificity. Using radio or fluorescence-labeled FAP-specific molecular probes can materialize high-contrast tumor imaging, and thereby facilitate early detection and monitoring. With regard to treatment, FAP-targeting strategies like FAP enzyme activity inhibitors, FAP-specific Chimeric Antigen Receptor T-Cell (CAR-T) cells, and FAP vaccines have demonstrated tremendous potential to hinder tumor growth, lower tumor angiogenesis, and reinforce anti-tumor immunity. For strengthening efficacy and lessening damage to normal cells, these strategies can also be integrated with chemotherapy, radiotherapy, and immunotherapy. This article not only reviews the research progress of FAP in tumor diagnosis and treatment, but also explores its paramount role and potential in the tumor microenvironment.

摘要

成纤维细胞活化蛋白(FAP)作为一种与肿瘤微环境(TME)密切相关的分子,近年来受到了广泛关注。FAP是一种II型跨膜丝氨酸蛋白酶,主要在癌症相关成纤维细胞(CAF)中表达,在肿瘤生长、侵袭、转移和免疫逃逸过程中发挥着重要作用。FAP在90%以上的上皮癌中高表达,因其具有极高的敏感性和特异性,使其成为一种令人满意的诊断标志物。使用放射性或荧光标记的FAP特异性分子探针可以实现高对比度的肿瘤成像,从而有助于早期检测和监测。在治疗方面,FAP靶向策略,如FAP酶活性抑制剂、FAP特异性嵌合抗原受体T细胞(CAR-T)和FAP疫苗,已显示出在抑制肿瘤生长、降低肿瘤血管生成和增强抗肿瘤免疫力方面的巨大潜力。为了提高疗效并减少对正常细胞的损害,这些策略还可以与化疗、放疗和免疫疗法相结合。本文不仅综述了FAP在肿瘤诊断和治疗方面的研究进展,还探讨了其在肿瘤微环境中的重要作用和潜力。

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