Colorectal Neoplasia Pathogenesis in Normal Appearing Colonic Mucosa -A Perspective With Focus on Eicosanoid Signaling Pathways

Abstract

Colorectal cancer (CRC) is a major cause of cancer-related mortality, especially in the Western world, and its incidence is expected to increase in the years to come. Prevention and early detection are key strategies to improve CRC morbidity and mortality. Although pathogenesis is still not fully understood, several signaling pathways have been studied and some are associated with the development of colorectal neoplasia (CRN) and CRC. Further identification of individuals with an increased risk of developing CRN would allow optimization of surveillance programs and help guide pharmacological preventive strategies. This perspective review outlines signaling pathways, biomarkers, and related pharmacological targets potentially implicated in the pathogenesis of CRN. We present our research based on studies carried out in normal appearing colonic mucosa from patients with and without CRN. With a focus on arachidonic acid signaling pathways, and in contrast to many other studies on cell culture and CRN tissue samples, our research is based on fresh colonic biopsies from normal tissue and presents and documents alterations in the function, expression, and location of enzymes, receptors, and transporters potentially involved in CRN pathogenesis. Based on these findings, we suggest areas of focus for future research and drug development for prevention and maybe even treatment of CRN and CRC. Furthermore, based on our observations of the COX-1 enzyme, we also discuss the implications of this enzyme in the development of CRN.