Chemoprevention of Colorectal Cancer

Abstract

Colorectal cancer is a major cause of mortality and treatment costs are considerable. Advocating lifestyle modification, faecal occult blood testing and surveillance colonoscopy in appropriate populations are already in practice. A developing concept is chemoprevention. Several models of carcinogenesis in colorectal cancer have been developed and there is an increasing database on the major molecular mechanisms involved in carcinogenesis mainly from preclinical experiments and phase I trials. There have been several large epidemiological and observational studies to evaluate possible protective effects of >200 agents. More recently, case-control and cohort studies and well-conceived, phase II/III clinical trials have been done or are under way to evaluate putative chemopreventive agents including established drugs like aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), 5-aminosalicylates and statins; more controversial drugs like cyclo-oxygenase-2 (COX-2) inhibitors, ursodeoxycholic acid; various vitamins and micronutrients including calcium, selenium, folic acid, and dietary fibre, fat and protein content. Despite promising outcome in preclinical studies, there is currently very limited data from well-controlled and appropriately powered clinical studies. The most promising agents currently are aspirin, traditional NSAIDs and COX-2 inhibitors. The recent reports of cardiovascular risks of the COX-2 inhibitors and some traditional NSAIDs have resulted in stagnation of the field. Pending the expected release of results from several phase III trials in the near future, chemoprevention for colorectal cancer can only be practically considered in the very-high-risk population like those with familial adenomatous polyposis and ulcerative colitis, in conjunction with surveillance colonoscopy. This article reviews the major models of colorectal carcinogenesis, the concept of chemoprevention with special reference to colorectal cancer and the current state of clinical literature and the future direction of colorectal cancer chemoprevention for both researcher and clinician alike.

Metformin Suppresses Colorectal Aberrant Crypt Foci in a Short-term Clinical Trial

“…A paradigm shift from surveillance for early detection of cancer or adenomas (polypectomy) to new preventive strategies, including chemoprevention, is needed to lower the burden of this disease. Several large epidemiologic and/or clinical studies have evaluated the possible effects of more than 200 agents, including fiber, calcium, and nonsteroidal anti-inflammatory drugs including aspirin and selective cyclooxygenase-2 (COX-2) inhibitors, in protecting against CRC development (3). Nonsteroidal antiinflammatory drugs, especially COX-2 inhibitors alone or in combination, have shown the most promise for CRC risk reduction (4), but reports have revealed an increased risk of serious cardiovascular events associated with COX-2 inhibitor use (5,6).…”

Induction of differentiation of human leukemia cells by combinations of COX inhibitors and 1, 25-dihydroxyvitamin D3 involves Raf1 but not Erk 1/2 signaling

“…These compounds have been used for GI cancer chemoprevention, and are approved for human use, [13][14][15] so if effective in potentiating the anti-leukemic action of 1,25D, could be introduced to therapeutic regimens. The translational significance of this study was further increased by demonstrating that the COX-inhibitor plus 1,25D differentiation synergy is not limited to HL60 cells, but is evident to some degree in other human myeloid leukemia cells.…”

The Effect of Flavonoids in Soybean Products in Lymphocytes from IBD and Colon Cancer Patients After Treatment with Food Mutagens and Hydrogen Peroxide

“…It is believed that flavonoids operate through their antioxidant properties and responses of H 2 O 2 and HCA to quercetin, epicatechin and rutin observed throughout the study, support the hypothesis that food mutagens target DNA by generating ROS. Concepts such as chemoprevention specifically focus on the long-term use of protective agents like vitamins (Boursi et al, 2007;Das et al, 2007). As shown, flavonoids have impressive antioxidant properties and are able to effectively protect the integrity of lymphocytes' DNA from ROS induced by HCA, which would make them the ideal supplemental compounds to prevent the onset of cancer www.intechopen.com…”