Exploring the Inflammatory Pathogenesis of Colorectal Cancer

Abstract

Colorectal cancer is one of the most commonly diagnosed cancers worldwide. Traditionally, mechanisms of colorectal cancer formation have focused on genetic alterations including chromosomal damage and microsatellite instability. In recent years, there has been a growing body of evidence supporting the role of inflammation in colorectal cancer formation. Multiple cytokines, immune cells such T cells and macrophages, and other immune mediators have been identified in pathways leading to the initiation, growth, and metastasis of colorectal cancer. Outside the previously explored mechanisms and pathways leading to colorectal cancer, initiatives have been shifted to further study the role of inflammation in pathogenesis. Inflammatory pathways have also been linked to some traditional risk factors of colorectal cancer such as obesity, smoking and diabetes, as well as more novel associations such as the gut microbiome, the gut mycobiome and exosomes. In this review, we will explore the roles of obesity and diet, smoking, diabetes, the microbiome, the mycobiome and exosomes in colorectal cancer, with a specific focus on the underlying inflammatory and metabolic pathways involved. We will also investigate how the study of colon cancer from an inflammatory background not only creates a more holistic and inclusive understanding of this disease, but also creates unique opportunities for prevention, early diagnosis and therapy.

The Role of C-Type Lectin Receptor Signaling in the Intestinal Microbiota-Inflammation-Cancer Axis

“…By transferring human fecal microbiota to germ-free mice, a recent study found CRC-associated microbiota dysbiosis contributed to oncogenic epigenetic alterations by inducing more hypermethylated genes in murine colonic mucosa, and cumulative methylation index is an independent risk factor for CRC ( 156 ). In addition, many mycotoxins and fungal metabolites also directly promote carcinogenesis, for example, Candida albicans can product nitrosamine, acetaldehyde and candidalysin ( 157 ). Furthermore, a latest study has just found that not only bacterial microbiota (e.g., Fusobacterium ) but also fungal microbiota can affect chemotherapy resistance ( 158 ).…”

The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma—Recent Findings and Review

“…A growing number of studies report that inflammation can influence the dynamics and aggressiveness of still-forming malignancy [ 2 , 10 , 21 ]. Canonically, there are three main pathways of genetic instability and two morphological sequences of CRC carcinogenesis, which differ in pathogenesis and dynamics [ 10 , 23 , 24 ] ( Figure 1 ).…”

“…In settings of reduced apoptotic stimuli and enhanced proliferation, the risk of genetic error increases, leading to the initiation of carcinogenesis [ 2 , 6 ]. The disruption in the cytokine-mediated crosstalk between immune and epithelial cells in the large bowel seems to be a major factor driving chronic inflammation and leading to the initiation and progression of large bowel cancers [ 21 ]. Epidemic studies seem to partly support the hypothesis that chronic inflammation accelerates the formation of cancer because colitis-associated cancers develop in younger patients, are often localized in the right colon, and are characterized by shorter overall survival [ 22 ].…”

Hepatocellular Carcinoma: Understanding the Inflammatory Implications of the Microbiome

“…For example, hepatic exposure to gut-derived microbiota-associated molecular patterns (MAMPs), such as lipopolysaccharide (LPS), promote hepatic inflammation, fibrosis, proliferation, as well as activation of anti-apoptotic signals [ 50 ]. Specifically, these MAMPs play a significant role in the activation of host pattern recognition receptors (PRRs) in the liver, especially the Toll-like receptor family (TLRs) [ 51 ]. Various types of hepatic cells express TLR4 in particular, including Kupffer cells, hepatic stellate cells (HSCs), and endothelial cells.…”