Angiogenesis and the immune response as targets for the prevention and treatment of colorectal cancer (review).
The carcinogenic process in previously normal human colonic mucosa involves hyperproliferation and adenoma formation, but it is not known why only a tiny proportion of adenomas undergo malignant transformation. There is accumulating evidence in favour of the hypothesis that inflammatory processes are a prerequisite for the development of malignancy. The data include upregulation of mediators of the inflammatory response such as cyclooxygenase-2, the generation of inflammatory cytokines which result in induction of cell proliferation and inhibition of apoptosis, and chronic inflammation which may lead to the production of reactive species that damage DNA. Angiogenesis, the formation of new blood vessels from an existing vasculature, is generally regarded as essential to the late stages of carcinogenesis, allowing tumours to grow beyond 1-2 mm in diameter, invade and metastasise. In this communication, it is argued that angiogenesis is not only present before neoplastic transformation occurs, but that it is of relevance to inflammatory diseases that increase risk of developing colorectal cancer. It is proposed that intervention to prevent or treat colorectal cancer should be targeted at inhibiting inflammation, reducing angiogenesis and stimulating cell mediated immune responses.
Sharma
Ricky A
RA
University Department of Oncology, Leicester Royal Infirmary, Leicester LE1 5WW, UK. ras20@le.ac.uk
Dalgleish
Angus G
AG
Steward
William P
WP
O'Byrne
Kenneth J
KJ
D015179:Colorectal Neoplasms / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D009389:Neovascularization, Pathologic