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[成纤维细胞活化蛋白(FAP)作为抗肿瘤策略的潜在靶点。]

[FIBROBLAST ACTIVATION PROTEIN (FAP) AS A POSSIBLE TARGET OF THE ANTITUMOR STRATEGY.].

作者信息

Pleshkan V V, Alekseenko I V, Tyulkina D V, Kyzmich A I, Zinovyeva M V, Sverdlov E D

出版信息

Mol Gen Mikrobiol Virusol. 2016;34(3):90-97.

Abstract

This review was devoted to the use of the versatile component oftumoral stroma (fibroblast activation protein, FAP) as a target of the versatile tumor therapy. The tumor is a coevolution system, which includes the microenvironment or reactive stroma differing from the normal tissue by the phenotypic and genotypic features. Important elements of the tumor microenvironment are cancer-associated fibroblasts (CAFs), which contain typical marker FAP (serine proteinase with the enzymatic activity of dipeptidyl peptidase and endopeptidase). According to the literature, more than 90% of tumors contain FAP-positive activated fibroblasts. FAP is virtually absent in normal tissues, but it is present in the embryonic and tumor tissues, which makes it a selective and versatile model. In this work, basic approaches to affecting the CAF using FAP as a target were discussed. The use of FAP as a target provides an important advantage: its proteolytic activity can be used along with the protein-targeted agents. The main directions in the therapeutic use of FAP were discussed in this work.

摘要

本综述致力于探讨将肿瘤基质的多功能成分(成纤维细胞活化蛋白,FAP)用作多功能肿瘤治疗靶点的应用。肿瘤是一个协同进化系统,其包括在表型和基因型特征上不同于正常组织的微环境或反应性基质。肿瘤微环境的重要组成部分是癌症相关成纤维细胞(CAF),其含有典型标志物FAP(具有二肽基肽酶和内肽酶酶活性的丝氨酸蛋白酶)。据文献报道,超过90%的肿瘤含有FAP阳性的活化成纤维细胞。FAP在正常组织中几乎不存在,但存在于胚胎组织和肿瘤组织中,这使其成为一个具有选择性和多功能性的模型。在这项工作中,讨论了以FAP为靶点影响CAF的基本方法。将FAP用作靶点具有一个重要优势:其蛋白水解活性可与蛋白靶向药物一起使用。本工作讨论了FAP治疗应用的主要方向。

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