Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management

Dulai, Parambir S.; Sandborn, William J.; Gupta, Samir

doi:10.1158/1940-6207.capr-16-0124

Cited by 150 publications

(116 citation statements)

References 103 publications

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“…Although antitumor immune response has been harnessed as an effective form of immunotherapy, it has long been recognized that abnormally active immune cells in various inflammation states can lead to tumorigenesis. For example, two inflammatory bowel conditions, ulcerative colitis and Crohn disease, are known precursors for colorectal cancer (39). The delicate balance between the pro-and anti-inflammatory state that is essential for gut immune homeostasis is regulated by intestinal commensal microbes (40)(41)(42)(43).…”

Section: Role Of Microbial Metabolites In Suppressing Intestinal Inflmentioning

confidence: 99%

Microenvironmental Metabolism Regulates Antitumor Immunity

et al. 2019

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Metabolic reprogramming of cancer cells and the tumor microenvironment are emerging as key factors governing tumor growth, metastasis, and response to therapies including immune checkpoint inhibitors. It has been recognized that rapidly proliferating cancer cells, tumor-infiltrating lymphocytes, and vascular endothelial cells compete for oxygen and nutrients. Tumor cells and other cell types in the microenvironment not only compete for nutrients, but they also simultaneously produce immunosuppressive metabolites, leading to immune escape. In addition, commensal microbial metabolites can influence regulatory T cells and inflammation in the intestine, thus playing an essential role in cancer prevention or cancer promotion. In this review, we summarize recent advances on metabolic interactions among various cell types in the tumor microenvironment, with a focus on how these interactions affect tumor immunity. We also discuss the potential role of blood vessel metabolism in regulating immune cell trafficking and activation.

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Section: Role Of Microbial Metabolites In Suppressing Intestinal Inflmentioning

confidence: 99%

Microenvironmental Metabolism Regulates Antitumor Immunity

et al. 2019

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“…Additionally, inflammatory bowel disease (IBD), in particular ulcerative colitis, represents a separate entity in which the risk of CRC is increased. The incidence of CRC in IBD patients (i.e., colitis-associated cancer or CAC) was reported to be up to 60% higher than the general population [2]. Sporadic CRCs may also demonstrate a prominent inflammatory response, known as tumor-induced inflammation.…”

Section: Introductionmentioning

confidence: 99%

Inflammation and Colorectal Cancer

Long

Lundsmith

Hamilton

2017

Curr Colorectal Cancer Rep

141

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Colorectal cancer (CRC) is the fourth most common cancer in both men and women in the United States, resulting in over 55,000 deaths annually. Environmental and genetic factors influence the development of CRC, and inflammation is a critical hallmark of cancer that may arise from a variety of factors. Purpose of review While patients with inflammatory bowel disease (IBD) have a higher risk of developing CRC, sporadic CRCs may engender or be potentiated by inflammation as well. In this review, we focus on recent advances in basic and translational research utilizing murine models to understand the contribution of inflammatory signaling pathways to CRC. Recent findings We discuss advances in the utility of three-dimensional enteroid/colonoid/tumoroid cultures to understand immune-epithelial interactions in CRC, as well as the potential for utilizing patient-derived tumoroids for personalized therapies. Summary This review underscores the importance of understanding the complex molecular mechanisms underlying inflammation in sporadic CRC and highlights up-and-coming or new avenues for CRC biomarkers or therapies.

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“…However, the precise mechanisms linking inflammation and tumor growth still need to be clarified. For example, inflammatory bowel disease is correlated with a significantly higher risk of CRC development and worse prognosis than patients with less pronounced chronic inflammation . Furthermore, advanced CRC tumors are associated with high levels of inflammatory cytokines.…”

mentioning

confidence: 99%

“…For example, inflammatory bowel disease is correlated with a significantly higher risk of CRC development and worse prognosis than patients with less pronounced chronic inflammation. [4][5][6] Furthermore, advanced CRC tumors are associated with high levels of inflammatory cytokines. Therefore, inflammatory pathways represent a potential therapeutic target for CRC and other inflammation-associated cancers.…”

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confidence: 99%

Inhibition of MK2 suppresses IL‐1β, IL‐6, and TNF‐α‐dependent colorectal cancer growth

Ray

Berggren

Cruz

et al. 2017

Intl Journal of Cancer

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Colorectal cancer (CRC) development and progression is associated with chronic inflammation. We have identified the MAPK-activated protein kinase 2 (MK2) pathway as a primary mediator of inflammation in CRC. MK2 signaling promotes production of proinflammatory cytokines IL-1β, IL-6 and TNF-α. These cytokines have been implicated in tumor growth, invasion and metastasis. For the first time, we investigate whether MK2 inhibition can improve outcome in two mouse models of CRC. In our azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated CRC, MK2 inhibitor treatment eliminated murine tumor development. Using the implanted, syngeneic murine CRC cell line CT26, we observe significant tumor volume reduction following MK2 inhibition. Tumor cells treated with MK2 inhibitors produced 80% less IL-1β, IL-6 and TNF-α and demonstrated decreased invasion. Replenishment of downstream proinflammatory MK2-mediated cytokines (IL-1β, IL-6 and TNF-α) to tumors led to restoration of tumor proliferation and rapid tumor regrowth. These results demonstrate the importance of MK2 in driving proinflammatory cytokine production, its relevance to in vivo tumor proliferation and invasion. Inhibition of MK2 may represent an attractive therapeutic target to suppress tumor growth and progression in patients.

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Colorectal Cancer and Dysplasia in Inflammatory Bowel Disease: A Review of Disease Epidemiology, Pathophysiology, and Management

Cited by 150 publications

References 103 publications

Microenvironmental Metabolism Regulates Antitumor Immunity

Microenvironmental Metabolism Regulates Antitumor Immunity

Inflammation and Colorectal Cancer

Inhibition of MK2 suppresses IL‐1β, IL‐6, and TNF‐α‐dependent colorectal cancer growth

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