Strategies for prevention of colorectal cancer: Pharmaceutical and nutritional interventions

Abstract

Interventions designed to delay or prevent the development of invasive colorectal adenocarcinoma might result in a profound impact on the incidence of and mortality from colorectal cancer. Current developmental efforts focus in two major directions: identification and testing of combination-targeted signal transduction pathway modulators and development of nutriceuticals. Both approaches recognize the heterogeneity of the carcinogenesis process. Combinations of agents (eg, aspirin or sulindac with DFMO, calcium with fiber), which have complementary or synergistic mechanisms or agents with broad spectrum anti-carcinogenic effects can potentially improve upon the effects of single agents and account for redundant signal transduction pathways involved in uncontrolled growth of clonal cells. Preliminary data in rodent systems suggest nutriceuticals or standardized foodstuffs, which contain multiple components, many of which are not identified have synergistic anticarcinogenesis effects. Diet modulation or supplementation with known standardized foodstuffs may be ideal in individuals at risk for colorectal cancer. Current clinical models for colorectal cancer prevention focus upon a pathologic-surrogate endpoint (reducing the recurrence or emergence of adenomas). This surrogate, generally accepted at a regulatory level, might not represent the true malignant progression from normal colonic mucosa to the malignant phenotype. Could the intervention simply prevent the emergence of adenomas that would not have progressed to invasive neoplasia in any event? Despite this major weakness, the adenoma remains the regulatory endpoint for efficacy because the cancer event remains rare, even among individuals selected as high-risk epidemiology but without known, highly pressured genetic-based stress. Over the next decade, the emergence of molecular and proteomic profiling tools have the potential of selecting adenomas that will progress to adenocarcinomas and will allow for investigation to be focused on individuals at increased risk.

The cytotoxic effect of Bowman–Birk isoinhibitors, IBB1 and IBBD2, from soybean (Glycine max) on HT29 human colorectal cancer cells is related to their intrinsic ability to inhibit serine proteases

“…In CRC, one of the leading causes of cancer-related mortality in western countries, nutritional intervention offers great potential to delay or prevent the development of malignant processes; such an interventional strategy might result in a positive impact on the incidence of disease and mortality [28]. In this context, soybean BBI and related proteins have recently emerged as highly promising chemotherapeutic compounds within the GIT [3][4][5].…”

Identification and characterization of CAC1 as a novel CDK2-associated cullin

“…Epidemiologic investigation has shown that dietary, environmental and hereditary factors may play roles in the occurrence and development of colorectal cancer. 12,13 Molecular studies have also into specific details of the molecular mechanism warrant further investigation. In summary, CAC1 is highly expressed in colorectal cancer, and the expression status and localization of CAC1 protein show cyclic alteration with the cell cycle.…”

Scientific Evidence of Rice By-Products for Cancer Prevention: Chemopreventive Properties of Waste Products from Rice Milling on CarcinogenesisIn VitroandIn Vivo

“…Natural products and their compounds may act as a modulator of antitumorigenicity either as separate entities or by serving in synergism [ 22 ]. The combination of two or more components in drug design has also been proven to have clinically synergistic benefits against cancer treatment [ 23 ].…”