成纤维细胞活化蛋白-α(FAP)是一种II型跨膜丝氨酸蛋白酶,具有特定的内肽酶活性。鉴于其在上皮癌的活化基质成纤维细胞中已确立的选择性表达,虽然不在静止的成纤维细胞中,FAP作为诊断标志物和治疗靶标已经受到了大量的研究关注。胰腺癌的特征是大量的纤维化或增生性基质,导致快速发展,治疗抗性,和不良的临床结果。大量研究表明,FAP在癌细胞中的大量表达,循环肿瘤细胞,基质细胞,胰腺癌的癌症相关成纤维细胞(CAFs)与多种癌症相关的信号通路有关,有助于癌症进展,入侵,迁移,转移,免疫抑制,和对治疗的抵抗力。在这篇文章中,本文旨在系统综述FAP在胰腺癌中的研究进展,包括它作为诊断标记的效用,治疗潜力,并与预后相关。我们还描述了FAP过表达基质细胞的功能作用,特别是CAF,在肿瘤免疫和代谢微环境中,并总结了FAP过表达CAFs在胰腺癌进展和治疗耐药中的作用机制。此外,我们讨论了靶向过表达FAP的CAFs是否可以代表一种潜在的治疗策略,并描述了FAP靶向诊断成像探针的发展.最后,我们评估了有关胰腺癌中FAP的台-床旁翻译的新兴基础和临床研究.
Fibroblast activation protein-α (FAP) is a type II transmembrane serine protease that has specific endopeptidase activity. Given its well-established selective expression in the activated stromal fibroblasts of epithelial cancers, although not in quiescent fibroblasts, FAP has received substantial research attention as a diagnostic marker and therapeutic target. Pancreatic cancer is characterized by an abundant fibrotic or desmoplastic stroma, leading to rapid progression, therapeutic resistance, and poor clinical outcomes. Numerous studies have revealed that the abundant expression of FAP in cancer cells, circulating tumor cells, stromal cells, and cancer-associated fibroblasts (CAFs) of pancreatic adenocarcinoma is implicated in diverse cancer-related signaling pathways, contributing to cancer progression, invasion, migration, metastasis, immunosuppression, and resistance to treatment. In this article, we aim to systematically review the recent advances in research on FAP in pancreatic adenocarcinoma, including its utility as a diagnostic marker, therapeutic potential, and correlation with prognosis. We also describe the functional role of FAP-overexpressing stromal cells, particulary CAFs, in tumor immuno- and metabolic microenvironments, and summarize the mechanisms underlying the contribution of FAP-overexpressing CAFs in pancreatic cancer progression and treatment resistance. Furthermore, we discuss whether targeting FAP-overexpressing CAFs could represent a potential therapeutic strategy and describe the development of FAP-targeted probes for diagnostic imaging. Finally, we assess the emerging basic and clinical studies regarding the bench-to-bedside translation of FAP in pancreatic cancer.