Lipoxygenase and cyclooxygenase pathways and colorectal cancer prevention

Colorectal cancer is one of the commonest malignancies in both men and women. In spite of significant progress in screening and in surgical and therapeutic interventions, colorectal cancer (CRC) is still a major public health problem. Accumulating evidence suggests that targeting inflammatory pathways may provide protection against the development of CRC. Eicosanoids derived from the enzymes cyclooxygenase (COX) and lipoxygenase (LOX) may contribute to CRC carcinogenesis. Approaches for targeting COX-1 and COX-2 with traditional nonsteroidal anti-inflammatory agents or targeting COX-2 with specific inhibitors are highly successful at the preclinical and clinical levels; however, large-scale clinical applicability of these agents is limited owing to unwanted side effects. Emerging studies suggests that 5-LOX-derived leukotrienes may contribute to colon tumor development and risk of thrombotic events. Thus, developing drugs that target both 5-LOX and COX-2 may provide a safer strategy. In this review, we discuss evidence for the involvement of 5-LOX in colon tumor development and targeting 5-LOX and COX-2 with synthetic and naturally occurring agents for CRC prevention.