: 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.

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An increase in the free radicals or reactive oxygen species (ROS) production and/or reduced scavenging through impaired endogenous antioxidant enzymes could result in oxidative stress (OS). The elevated level of OS in the cells may result in extensive cellular damage to molecules with double bond, viz., membrane phospholipid and nucleic acids such as DNA, RNA, and other macromolecules, that ultimately leads to apoptosis or necrosis. Exposure to environmental contaminants and virus could augment the production of ROS and result in the development of cancer. The increase of ROS levels is reported during various physiological and pathological conditions, such as aging, stress, inflammation, rheumatoid arthritis, respiratory disorders, diabetes, myocardial infarction, and cancer. This book chapter is focused to discuss several aspects of endogenous antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), their relevance in the initiation of oncogenesis, epithelialmesenchymal transition (EMT), and carcinogenesis. Several drugs, which primarily utilize antioxidant enzymes to mediate anticancer activities, are also discussed in this chapter. Further, the chapter also collates the information regarding antioxidant enzyme mimics to circumvent several cancer types.

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