Role of Inflammation in the Development of Colorectal Cancer

Abstract

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes

“…Furthermore, in our cohort we also observed 30% of cases and 40% of cases with CCND1 and MYC gene alterations, respectively. Anomalous NLRP3 expression was reported in different tumors [8,9,33,34], and it's up-regulation in breast cancer-associated fibroblasts (CAFs) is related to cancer progression and metastasis [35]. A strong correlation of NLRP3, PYCARD and CyclinD1 with hormone status was observed in our samples, suggesting a possible association with the Luminal phenotype.…”

Methylglyoxal Levels in Human Colorectal Precancer and Cancer: Analysis of Tumor and Peritumor Tissue

“…Many cytokines that are produced by intestinal immune cells during or in response to local inflammation in the colon and rectum, can stimulate complex interactions between different cell types in the intestinal environment, leading to acute inflammation [36]. Inflammation has been shown induce the occurrence and progression of CRC [37].…”

Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients

“…Inflammasome components are involved in different physiological and pathological conditions, and their contribution in different cancers has been highlighted in the past few years (9)(10)(11)(12). The role of inflammasomes in cancer is dual.…”