Chemoprevention of Colorectal Cancer in High-Risk Patients: from Molecular Targets to Clinical Trials

Abstract An increased understanding of the molecular pathways involved in colorectal carcinogenesis has helped researchers to develop possible chemopreventive strategies. This has been of particular relevance for high-risk subjects, for whom chemopreventive strategies may be helpful in slowing cancer development. In order to obtain more definitive data on chemopreventive agents, there has been a great effort to develop preclinical models that resemble the clinical scenarios encountered in high-risk patients. Importantly, many compounds, in particular non-steroidal anti-inflammatory drugs, have shown significant effects in models of highrisk clinical settings. However, results from clinical trials have been somewhat disappointing and no definitive chemopreventative agent is currently given for any of the high-risk conditions. In this review, we examine the available data on the effects of chemopreventive drugs on molecular targets relevant for high-risk conditions predisposing to colorectal cancer, including data from preclinical studies that have led to clinical trials.