Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases.
Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases.
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DOI：
10.7150/thno.15625
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发表时间：
2017
期刊：
影响因子：
12.4
通讯作者：
Neamati N
中科院分区：
文献类型：
--
作者：
Ha H;Debnath B;Neamati N
趋化因子受体CXCR1/2及其配体CXCL8对于炎症介质的激活和转运以及肿瘤的进展和转移至关重要。CXCL8-CXCR1/2信号轴参与多种疾病的发病机制，包括慢性阻塞性肺疾病（COPD）、哮喘、囊性纤维化和癌症。特定癌细胞分泌的CXCL8与肿瘤微环境中CXCR1/2的相互作用对癌症的进展和转移至关重要。CXCL8-CXCR1/2轴可能通过调节肿瘤干细胞（CSC）增殖和自我更新在肿瘤进展和转移中发挥重要作用。在过去的二十年中，已经报道了几种小分子CXCR1/2抑制剂，CXCL8释放抑制剂以及针对CXCL8和CXCR1/2的中和抗体。作为单药，这类抑制剂有望对各种炎症性疾病有效。一些临床前研究表明，CXCR1/2抑制剂联合其他靶向治疗、化疗和免疫治疗可能有效治疗某些癌症。目前，这些抑制剂中有几种正处于COPD、哮喘和转移性乳腺癌的晚期临床试验中。在这篇综述中，我们全面分析了CXCL8-CXCR1/2轴在疾病进展中的作用，并选择了在该途径中共表达的基因。我们还讨论了针对这一途径开发小分子药物的最新进展。
The chemokine receptors CXCR1/2 and their ligand CXCL8 are essential for the activation and trafficking of inflammatory mediators as well as tumor progression and metastasis. The CXCL8-CXCR1/2 signaling axis is involved in the pathogenesis of several diseases including chronic obstructive pulmonary diseases (COPD), asthma, cystic fibrosis and cancer. Interaction between CXCL8 secreted by select cancer cells and CXCR1/2 in the tumor microenvironment is critical for cancer progression and metastasis. The CXCL8-CXCR1/2 axis may play an important role in tumor progression and metastasis by regulating cancer stem cell (CSC) proliferation and self-renewal. During the past two decades, several small-molecule CXCR1/2 inhibitors, CXCL8 releasing inhibitors, and neutralizing antibodies against CXCL8 and CXCR1/2 have been reported. As single agents, such inhibitors are expected to be efficacious in various inflammatory diseases. Several preclinical studies suggest that combination of CXCR1/2 inhibitors along with other targeted therapies, chemotherapies, and immunotherapy may be effective in treating select cancers. Currently, several of these inhibitors are in advanced clinical trials for COPD, asthma, and metastatic breast cancer. In this review, we provide a comprehensive analysis of the role of the CXCL8-CXCR1/2 axis and select genes co-expressed in this pathway in disease progression. We also discuss the latest progress in developing small-molecule drugs targeting this pathway.
影响因子：
2.4
作者：
Leung, Sarah J.;Rice, Photini S.;Barton, Jennifer K.
通讯作者：
Barton, Jennifer K.