Chronic immune activation and inflammation as the cause of malignancy.
Several chronic infections known to be associated with malignancy have established oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associated with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development of malignancy. This environment includes upregulation of mediators of the inflammatory response such as cyclo-oxygenase (COX)-2 leading to the production of inflammatory cytokines and prostaglandins which themselves may suppress cell mediated immune responses and promote angiogenesis. These factors may also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers.
O'Byrne
K J
KJ
Department of Oncology, University of Leicester, Leicester, UK.
Dalgleish
A G
AG
D002471:Cell Transformation, Neoplastic; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation; D007527:Isoenzymes / Q000378:metabolism; D008315:Malondialdehyde / Q000494:pharmacology; D008565:Membrane Proteins; D009369:Neoplasms / Q000209:etiology*; D009389:Neovascularization, Pathologic; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology
D016207:Cytokines; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases