Title:Role of Inflammation in the Development of Colorectal Cancer
Volume: 21
Issue: 1
Author(s): Sridhar Muthusami, Ileng Kumaran Ramachandran*, Kokelavani Nampalli Babu, Sneha Krishnamoorthy, Akash Guruswamy, Lurdes Queimado, Gautam Chaudhuri and Ilangovan Ramachandran*
Affiliation:
- Biology Department, Farmingdale State College, Farmingdale, NY 11735,United States
- Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095,United States
Keywords:
Aptamer, colitis, colorectal cancer (CRC), cytokines, inflammasomes, inflammation, inflammatory bowel disease
(IBD), interleukin (IL), microRNA (miRNA/miR), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB),
small activating RNA (saRNA), tumor necrosis factor-alpha (TNF-α), ulcerative colitis (UC).
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, have 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 pro-inflammatory 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 pro-inflammatory 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 inflammation-associated CRC by using monoclonal antibodies
or aptamers to block pro-inflammatory molecules, inhibitors of tyrosine kinases in the inflammatory
signaling cascade, competitive inhibitors of pro-inflammatory molecules, and the nucleic
acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor
suppressor or repress oncogene/pro-inflammatory cytokine gene expression.
