Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248 Paris, France; Inserm, U830, 26, rue d'Ulm, Paris, F-75005 France.
Nuclear Medicine Department, Institut Curie Hospital Group, 35 rue Dailly, 92210 Saint-Cloud, France; Laboratoire d'Imagerie Translationnelle en Oncologie (LITO), U1288 Inserm, Institut Curie, Orsay, France.
Semin Cancer Biol. 2022 Nov;86(Pt 3):262-272. doi: 10.1016/j.semcancer.2022.04.008. Epub 2022 Apr 27.
Cancer-Associated Fibroblasts (CAFs) represent the most prominent component of the tumor microenvironment (TME). Recent studies demonstrated that CAF are heterogeneous and composed of different subpopulations exerting distinct functions in cancer. CAF populations differentially modulate various aspects of tumor growth, including cancer cell proliferation, extra-cellular matrix remodeling, metastatic dissemination, immunosuppression and resistance to treatment. Among other markers, the Fibroblast Activation Protein (FAP) led to the identification of a specific CAF subpopulation involved in metastatic spread and immunosuppression. Expression of FAP at the surface of CAF is detected in many different cancer types of poor prognosis. Thus, FAP recently appears as an appealing target for therapeutic and molecular imaging applications. In that context, Ga-labeled radiopharmaceutical-FAP-inhibitors (FAPI) have been recently developed and validated for quantitatively mapping FAP expression over the whole-body using Positron Emission Tomography (PET/CT). In this review, we describe the main current knowledge on CAF subpopulations and their distinct functions in solid tumors, as well as the promising diagnostic and therapeutic implications of radionuclides targeting FAP.
癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）中最主要的组成部分。最近的研究表明，CAF 具有异质性，并由不同的亚群组成，这些亚群在癌症中发挥着不同的功能。CAF 群体在不同程度上调节着肿瘤生长的各个方面，包括癌细胞增殖、细胞外基质重塑、转移扩散、免疫抑制和治疗耐药性。除了其他标志物之外，成纤维细胞激活蛋白（FAP）导致了一种特定的 CAF 亚群的鉴定，该亚群参与转移扩散和免疫抑制。在预后不良的许多不同癌症类型中，CAF 表面的 FAP 表达被检测到。因此，FAP 最近似乎成为治疗和分子成像应用的有吸引力的靶点。在这种情况下，Ga 标记的放射性药物-FAP 抑制剂（FAPI）已被最近开发并验证，可用于使用正电子发射断层扫描（PET/CT）对全身的 FAP 表达进行定量成像。在这篇综述中，我们描述了 CAF 亚群的主要当前知识及其在实体瘤中的不同功能，以及靶向 FAP 的放射性核素在诊断和治疗方面的有希望的应用。
