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Therapeutics targeting innate immune/inflammatory responses through the interleukin-6/JAK/STAT signal transduction pathway in patients with cancer

  • Campbell S.D. Roxburgh
    Affiliations
    Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom
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  • Donald C. McMillan
    Correspondence
    Reprint requests: Donald C. McMillan, Academic Department of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow G31 2ER, United Kingdom
    Affiliations
    Academic Unit of Surgery, School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom
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Published:September 15, 2015DOI:https://doi.org/10.1016/j.trsl.2015.08.013
      Over the last 15 years, there has been an evolution in the thinking of how tumors grow and disseminate: from the earlier work where it was considered that the intrinsic characteristics of the tumor largely determined the process to more recent work where local and systemic inflammatory responses play a key role in disease progression and survival in patients with cancer. Although the immune/inflammatory responses to cancer are complex, it is clear that targeting the host immune/inflammatory responses (in particular, innate/humoral responses) has considerable potential to improve outcomes in patients with a variety of common solid tumors. There are a wide variety of agents from the nonselective glucocorticoids to the selective Janus Activated Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors that has considerable therapeutic potential. They may be considered to act through a main signal transduction mechanism, the interleukin-6/JAK/STAT pathway. This work heralds a new era in which it will be important not only to treat the tumor but also to treat the host, so called oncoimmunology.

      Abbreviations:

      JAK (Janus Activated Kinase), STAT (Signal Transducer and Activator of Transcription), EGF (epidermal growth factor), TGF-B (transforming growth factor beta), VEGF (vascular endothelial growth factor), TNF-a (tumour necrosis factor alpha), CRP (C-reactive protein), COX (cyclooxygenase), TNM (tumour node metastases), CD3 (Type I transmembrane protein found on T-lymphocytes), AOM-DSS (azoxymethane- dextran sodium sulphate)
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