Interleukin-6 and colorectal cancer development

Abstract

Background. Colorectal cancer (CRC) is one of the most common malignancies in the world. It ranks third in the structure of cancer morbidity and second in the structure of mortality. One of the important factors leading to CRC is chronic inflammation of the intestine, in which pro-inflammatory cytokines play a crucial role. Among proinflammatory cytokines, interleukin-6 occupies one of the leading places in the pathogenesis of CRC. Therefore, it is important to elucidate the role of interleukin-6 (IL-6) in the development and progression of CRC, determine the diagnostic and prognostic value of the cytokine and analyze the application of therapeutic strategies aimed at the IL-6 signaling pathway in CRC. Purpose – to analyze the role of proinflammatory cytokine IL-6 in the development of colorectal cancer, consider the mechanisms of oncogenic action of cytokine, evaluate the results of therapeutic strategies aimed at the IL-6 signaling pathway in colorectal cancer and characterize prognostic and diagnostic value of IL-6. Data sources. Data search for review was performed in databases Pubmed, Cochrane Library, ScienceDirect. The results of research performed before May 2021 are analyzed. Relevant unpublished studies have been found in clinical trial registry of U.S. National Institutes of Health www.clinicaltrials.gov. Results. The assessment of diagnostic and prognostic value of IL-6 in patients with CRC is given. The mechanisms of IL-6 regulation of tumor growth, angiogenesis, apoptosis, metastasis in CRC are elucidated. The results of preclinical and clinical testing of monoclonal antibodies to IL-6, IL-6R, low molecular weight compounds that affect cytokine receptor signaling through gp130 and JAK-STAT, as well as drugs and compounds of natural origin, that are able to inhibit IL-6/STAT3 signal pathway, are presented. Conclusions. Strategies to block IL-6 signaling may be potentially useful in malignancies, most likely as a component of combination therapy, or in preventing adverse symptoms associated with cancer immunotherapy. Further research is needed to elucidate the exact role of classical IL-6 signaling and trans-signaling in the pathogenesis of colorectal cancer, as this may provide a basis for more targeted inhibition of the functions of this pleiotropic cytokine.