Interleukin-6 signaling pathway in targeted therapy for cancer

  • Yuqi Guo
    Affiliations
    The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China

    Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA
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  • Feng Xu
    Affiliations
    The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, PR China

    Biomedical Engineering and Biomechanics Center, Xi’an Jiaotong University, Xi’an, PR China
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  • TianJian Lu
    Affiliations
    The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, PR China

    Biomedical Engineering and Biomechanics Center, Xi’an Jiaotong University, Xi’an, PR China
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  • Zhenfeng Duan
    Affiliations
    Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA
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  • Zhan Zhang
    Correspondence
    Corresponding author. Address: Department of Obstetrics and Gynecology, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China. Tel.: +11 86 371 66991970; fax: +11 86 371 66991971.
    Affiliations
    The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China

    Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA
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      Summary

      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.

      Keywords

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