趋化因子及其对应的受体组成了一个复杂的信号网络，被癌细胞利用来促进不可控的肿瘤生长和扩散。ACKR3（非经典趋化因子受体3），传统上称为CXCR7，在许多癌症中被上调表达，包括晚期前列腺癌，是治疗干预的有希望的靶点。与CXCR4等典型的G蛋白偶联受体不同，CXCR7一旦被其对应的配基CXCL12所结合，会启动β-阻滞素的招募而非G蛋白，导致CXCL12的快速内化和降解，起到清除受体的作用。然而，最近的证据表明，CXCR7可能不仅是CXCR4的清除受体或辅助受体，还可能在调节癌症进展中发挥重要作用，其中一些作用是独立于CXCR4及其配基，如CXCL12的。持续活性的CXCR7会结合β-阻滞素。这个蛋白质复合物内化形成一个支架，用于组装和激活各种细胞质激酶，对细胞存活和肿瘤生长至关重要。在本文中，我们回顾和讨论了关于CXCR7调控和功能的最新知识，以及这种新认识如何指导CXCR7抑制剂的开发，重点放在前列腺癌上。© 2023。作者，独家授权给Springer Nature Limited。

Chemokines and their cognate receptors comprise an intricate signaling network that becomes high-jacked by cancer cells for uncontrollable tumor growth and dissemination. ACKR3 (Atypical Chemokine Receptor 3), traditionally called CXCR7, is up-regulated in many cancers, including advanced prostate cancer, and represents promising targets for therapeutic intervention. Unlike typical G protein-coupled receptors such as CXCR4, CXCR7, once bound by its cognate ligand CXCL12, initiates the recruitment of β-arrestin instead of G proteins, and results in rapid internalization and degradation of CXCL12, functioning as a scavenger receptor. However, recent evidence suggests that CXCR7 may be more than a scavenger or auxiliary receptor of CXCR4 and that it may play essential roles in regulating cancer progression, some of which are independent of CXCR4 and its ligands, such as CXCL12. Constitutively active CXCR7 binds to β-arrestin. This protein complex internalizes to form a scaffold for assembling and activating various cytoplasmic kinases necessary for cell survival and tumor growth. Here we review and discuss the up-to-date knowledge on CXCR7 regulation and function and how this new understanding guides the development of CXCR7 inhibitors, focusing on prostate cancer.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.