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从基础研究到临床应用:以成纤维细胞激活蛋白为靶点进行癌症诊断和治疗。

From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.

机构信息

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing, 100730, China.

出版信息

Cell Oncol (Dordr). 2024 Apr;47(2):361-381. doi: 10.1007/s13402-023-00872-z. Epub 2023 Sep 19.

Abstract

PURPOSE

This study aims to review the multifaceted roles of a membrane protein named Fibroblast Activation Protein (FAP) expressed in tumor tissue, including its molecular functionalities, regulatory mechanisms governing its expression, prognostic significance, and its crucial role in cancer diagnosis and treatment.

METHODS

Articles that have uncovered the regulatory role of FAP in tumor, as well as its potential utility within clinical realms, spanning diagnosis to therapeutic intervention has been screened for a comprehensive review.

RESULTS

Our review reveals that FAP plays a pivotal role in solid tumor progression by undertaking a multitude of enzymatic and nonenzymatic roles within the tumor stroma. The exclusive presence of FAP within tumor tissues highlights its potential as a diagnostic marker and therapeutic target. The review also emphasizes the prognostic significance of FAP in predicting tumor progression and patient outcomes. Furthermore, the emerging strategies involving FAPI inhibitor (FAPI) in cancer research and clinical trials for PET/CT diagnosis are discussed. And targeted therapy utilizing FAP including FAPI, chimeric antigen receptor (CAR) T cell therapy, tumor vaccine, antibody-drug conjugates, bispecific T-cell engagers, FAP cleavable prodrugs, and drug delivery system are also introduced.

CONCLUSION

FAP's intricate interactions with tumor cells and the tumor microenvironment make it a promising target for diagnosis and treatment. Promising strategies such as FAPI offer potential avenues for accurate tumor diagnosis, while multiple therapeutic strategies highlight the prospects of FAP targeting treatments which needs further clinical evaluation.

摘要

目的

本研究旨在综述一种在肿瘤组织中表达的膜蛋白——成纤维细胞激活蛋白(FAP)的多方面作用,包括其分子功能、调控其表达的机制、预后意义及其在癌症诊断和治疗中的关键作用。

方法

筛选了揭示 FAP 在肿瘤中调控作用及其在临床领域潜在应用的文章,进行了全面综述。

结果

我们的综述揭示了 FAP 通过在肿瘤基质中发挥多种酶和非酶作用,在实体瘤进展中起着关键作用。FAP 仅存在于肿瘤组织中,这突出了其作为诊断标志物和治疗靶点的潜力。该综述还强调了 FAP 在预测肿瘤进展和患者预后方面的预后意义。此外,还讨论了涉及 FAPI 抑制剂(FAPI)在癌症研究和临床试验中的 PET/CT 诊断的新兴策略。并介绍了针对 FAP 的靶向治疗,包括 FAPI、嵌合抗原受体(CAR)T 细胞疗法、肿瘤疫苗、抗体药物偶联物、双特异性 T 细胞衔接器、FAP 可裂解前药和药物传递系统。

结论

FAP 与肿瘤细胞和肿瘤微环境的复杂相互作用使其成为诊断和治疗的有前途的靶点。有前途的策略,如 FAPI,为准确的肿瘤诊断提供了潜在途径,而多种治疗策略则突出了针对 FAP 的靶向治疗的前景,需要进一步的临床评估。

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