Oncology Department, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain.
Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
J Leukoc Biol. 2021 May;109(5):953-967. doi: 10.1002/JLB.5BT1219-714R. Epub 2020 Oct 22.
The chemokine receptor, C-X-C chemokine receptor type 4 (CXCR4) and its ligand, C-X-C motif chemokine 12, are key mediators of hematopoietic cell trafficking. Their roles in the proliferation and metastasis of tumor cells, induction of angiogenesis, and invasive tumor growth have been recognized for over 2 decades. CXCR4 is a promising target for imaging and therapy of both hematologic and solid tumors. To date, Sanofi Genzyme's plerixafor is the only marketed CXCR4 inhibitor (i.e., Food and Drug Administration-approved in 2008 for stem cell mobilization). However, several new CXCR4 inhibitors are now being investigated as potential therapies for a variety of fluid and solid tumors. These small molecules, peptides, and Abs include balixafortide (POL6326, Polyphor), mavorixafor (X4P-001, X4 Pharmaceuticals), motixafortide (BL-8040, BioLineRx), LY2510924 (Eli Lilly), and ulocuplumab (Bristol-Myers Squibb). Early clinical evidence has been encouraging, for example, with motixafortide and balixafortide, and the CXCR4 inhibitors appear to be generally safe and well tolerated. Molecular imaging is increasingly being used for effective patient selection before, or early during CXCR4 inhibitor treatment. The use of radiolabeled theranostics that combine diagnostics and therapeutics is an additional intriguing approach. The current status and future directions for radioimaging and treating patients with CXCR4-expressing hematologic and solid malignancies are reviewed. See related review - At the Bench: Pre-Clinical Evidence for Multiple Functions of CXCR4 in Cancer. J. Leukoc. Biol. xx: xx-xx; 2020.
趋化因子受体 C-X-C 趋化因子受体 4（CXCR4）及其配体 C-X-C 基序趋化因子 12 是造血细胞迁移的关键介质。它们在肿瘤细胞的增殖和转移、血管生成的诱导以及侵袭性肿瘤生长中的作用已经被认识了 20 多年。CXCR4 是成像和治疗血液系统和实体肿瘤的有前途的靶点。迄今为止，赛诺菲健赞的培立噻吩（plerixafor）是唯一上市的 CXCR4 抑制剂（即 2008 年获得美国食品和药物管理局批准用于干细胞动员）。然而，目前有几种新型 CXCR4 抑制剂正在被研究作为多种液体和实体肿瘤的潜在治疗方法。这些小分子、肽和 Abs 包括贝利昔芬（POL6326，Polyphor）、莫替昔芬（X4P-001，X4 Pharmaceuticals）、莫替昔芬（BL-8040，BioLineRx）、LY2510924（礼来）和乌洛昔单抗（百时美施贵宝）。早期的临床证据令人鼓舞，例如，莫替昔芬和贝利昔芬，并且 CXCR4 抑制剂似乎通常是安全和耐受良好的。分子成像越来越多地用于在 CXCR4 抑制剂治疗之前或早期对患者进行有效选择。结合诊断和治疗的放射性标记治疗学的使用是另一种有趣的方法。本文综述了用于治疗表达 CXCR4 的血液系统和实体恶性肿瘤患者的放射性成像和治疗的现状和未来方向。另见相关综述 - 在实验室：CXCR4 在癌症中的多种功能的临床前证据。J. Leukoc. Biol. xx: xx-xx; 2020.
