Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer.
Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer.
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DOI：
10.18632/oncotarget.7102
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发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Suh N
中科院分区：
文献类型：
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作者：
Heo TH;Wahler J;Suh N
白介素 6 (IL-6) 是一种多效性细胞因子，在免疫调节、炎症和肿瘤发生中具有已知的多种功能。 IL-6 与 IL-6 受体 (IL-6R) 的结合诱导同二聚化和糖蛋白 130 (gp130) 的募集，从而导致下游信号传导的激活。新的证据表明，高水平的 IL-6 与乳腺癌患者的不良预后相关。 IL-6 似乎在乳腺癌细胞的生长和转移、乳腺癌干细胞 (BCSC) 的更新和 BCSC 的耐药性中发挥着关键作用，这使得抗 IL-6/IL-6R/gp130 疗法成为治疗和预防乳腺癌的有希望的选择。然而，抗IL-6/IL-6R/gp130疗法在乳腺癌中的应用的临床前和临床研究有限。在这篇综述中，我们总结了直接结合 IL-6、IL-6R 或 gp130 的化学和生物阻断剂的结构、临床前和临床研究、作用机制，以及这些药物作为乳腺癌治疗的潜在临床应用。
Interleukin-6 (IL-6) is a pleiotropic cytokine with known multiple functions in immune regulation, inflammation, and oncogenesis. Binding of IL-6 to the IL-6 receptor (IL-6R) induces homodimerization and recruitment of glycoprotein 130 (gp130), which leads to activation of downstream signaling. Emerging evidence suggests that high levels of IL-6 are correlated with poor prognosis in breast cancer patients. IL-6 appears to play a critical role in the growth and metastasis of breast cancer cells, renewal of breast cancer stem cells (BCSCs), and drug resistance of BCSCs, making anti–IL-6/IL-6R/gp130 therapies promising options for the treatment and prevention of breast cancers. However, preclinical and clinical studies of the applications of anti–IL-6/IL-6R/gp130 therapy in breast cancers are limited. In this review, we summarize the structures, preclinical and clinical studies, mechanisms of action of chemical and biological blockers that directly bind to IL-6, IL-6R, or gp130, and the potential clinical applications of these pharmacological agents as breast cancer therapies.