Cytokines, inflammation and colon cancer.
Patients with inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, are at increased risk of developing colon cancer, confirming that chronic inflammation predisposes to development of tumors. Moreover, it appears that colon cancers that do not develop as a complication of inflammatory bowel disease are also driven by inflammation, because it has been shown that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) lowers the mortality from sporadic colon cancer and results in regression of adenomas in familial adenomatous polyposis (FAP) patients, who inherit a mutation in the Apc gene. Colorectal cancer therefore represents a paradigm for the link between inflammation and cancer. Inflammation is driven by soluble factors, cytokines and chemokines, which can be produced by tumor cells themselves or, more often, by the cells recruited to the tumor microenvironment. Inflammatory cytokines and chemokines promote growth of tumor cells, perturb their differentiation, and support the survival of cancer cells. Tumor cells become addicted to inflammatory stroma, suggesting that the tumor microenvironment represents an attractive target for preventive and therapeutic strategies. Proinflammatory cytokines, such as TNFα, IL-6 and IL-1β, or transcription factors that are required for signaling by these cytokines, including NF-κB and STATs, are indeed emerging as potential targets for anticancer therapy. TNFα antagonists are in phase I/II clinical trials and have been shown to be well tolerated in patients with solid tumors, and IL-1β antagonists that ameliorate several inflammatory disorders characterized by excessive IL-1β production, will likely follow. Therefore, development of drugs that normalize the tumor microenvironment or interrupt the crosstalk between the tumor and the tumor microenvironment is an important approach to the management of cancer.
Albert Einstein Cancer Center, Montefiore Medical Center, Department of Oncology, Bronx, NY 10467, USA. lidija.klampfer@einstein.yu.edu
Lidija
L
Klampfer
D000818:Animals; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D016207:Cytokines
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