Department of General Pathology and Excellence Research Centre on Cardiovascular Diseases, 1st School of Medicine, Second University of Naples, Complesso S. Andrea delle Dame, Via Costantinopoli 16, Naples, 80138, Italy.
Recent Pat Anticancer Drug Discov. 2012 Sep;7(3):251-64. doi: 10.2174/157489212801820039.
CXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue and is involved in the outgrowth and metastasis of CXCR4 expressing tumors. Recent investigations have indicated that CXCL12 levels increase after chemo- and anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has emerged as a potential additional or alternative target for neo-adjuvant treatments. We have reviewed recent patent applications between 2008 and 2011 in tumor angiogenesis and the most clinical data supporting the potential use of anti-CXCR4 agents in this field. Among these, AMD3100, also known as Plerixaform (Mozobil by Genzyme), is approved for stem cell mobilisation in patients with leukaemia, while BKT140 (Emory University), POL6326 (Polyphor Ag) and TG-0054 (ChemoCentryx) are currently in clinical trials in combination with chemotherapy for multiple myeloma and leukaemia. The aptamer Nox-A12 (Noxxon) is in trials for chronic lymphatic leukaemia treatment. MSX-122 (Metastatix) is in Phase I trials for solid tumor treatment, while CXCR7-specific inhibitor CCX2066 (ChemoCentryx) is still in preclinical studies. We have also considered other strategies, such RNA interference and miRNA, which could be tested for solid tumor adjuvant therapy.
趋化因子配体 12（也称为 SDF-1）是趋化因子受体 CXCR4 和 CXCR7 的唯一天然配体。在正常内皮组织中，CXCL12 具有血管生成特性，并且与表达 CXCR4 的肿瘤的生长和转移有关。最近的研究表明，在化疗和抗 VEGF 治疗后，CXCL12 水平增加，有利于复发。阻断 CXCL12/CXCR4 轴已成为新辅助治疗的潜在附加或替代靶标。我们回顾了 2008 年至 2011 年间肿瘤血管生成的最新专利申请和最支持在该领域使用抗 CXCR4 药物的临床数据。其中，AMD3100，也称为普乐沙福（安进公司的 Mozobil），已获准用于白血病患者的干细胞动员，而 BKT140（埃默里大学）、POL6326（百拓利）和 TG-0054（ChemoCentryx）目前正在临床试验中，与化疗联合用于多发性骨髓瘤和白血病。适体 Nox-A12（Noxxon）正在进行慢性淋巴细胞白血病治疗的临床试验。MSX-122（Metastatix）正在进行实体瘤治疗的 I 期临床试验，而 CXCR7 特异性抑制剂 CCX2066（ChemoCentryx）仍处于临床前研究阶段。我们还考虑了其他策略，例如 RNA 干扰和 miRNA，这些策略可用于实体瘤辅助治疗。
