The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China.
Cancer Treat Rev. 2012 Nov;38(7):904-10. doi: 10.1016/j.ctrv.2012.04.007. Epub 2012 May 29.
Interleukin-6 (IL-6) is a multifunctional cytokine which plays an important role in a wide range of biologic activities in different types of cell including tumor cells. IL-6 is involved in the host immune defense mechanism as well as the modulation of growth and differentiation in various malignancies. These effects are mediated by several signaling pathways, in particular the signal transducer and transcription activator 3 (Stat3). There exists abundant evidence demonstrating that deregulated overexpression of IL-6 was associated with tumor progression through inhibition of cancer cell apoptosis, stimulation of angiogenesis, and drug resistance. Clinical studies have revealed that increased serum IL-6 concentrations in patients are associated with advanced tumor stages of various cancers (e.g., multiple myeloma, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, prostate cancer, breast cancer and ovarian cancer) and short survival in patients. Therefore, blocking IL-6 signaling is a potential therapeutic strategy for cancer (i.e., anti-IL-6 therapy) characterized by pathological IL-6 overproduction. Preliminary clinical evidence has shown that antibody targeted IL-6 therapy was well tolerated in cancer patients. In this review, we detail the progress of the current understanding of IL-6 signaling pathway in cancer as well as an antibody targeted IL-6 therapy for human cancer.
白细胞介素-6 (IL-6) 是一种多功能细胞因子，在包括肿瘤细胞在内的不同类型的细胞中，广泛的生物学活性中发挥重要作用。IL-6 参与宿主免疫防御机制，以及各种恶性肿瘤的生长和分化的调节。这些作用是通过几种信号通路介导的，特别是信号转导子和转录激活子 3 (Stat3)。有大量证据表明，IL-6 的失调过表达通过抑制癌细胞凋亡、刺激血管生成和耐药性与肿瘤进展有关。临床研究表明，患者血清中 IL-6 浓度的增加与各种癌症（例如多发性骨髓瘤、非小细胞肺癌、结直肠癌、肾细胞癌、前列腺癌、乳腺癌和卵巢癌）的晚期肿瘤阶段和患者的短生存期有关。因此，阻断 IL-6 信号是癌症的一种潜在治疗策略（即抗 IL-6 治疗），其特征是病理性 IL-6 过度产生。初步临床证据表明，针对 IL-6 的抗体靶向治疗在癌症患者中具有良好的耐受性。在这篇综述中，我们详细介绍了当前对癌症中 IL-6 信号通路的理解以及针对人类癌症的 IL-6 抗体靶向治疗的进展。
