Targeting the Leukotriene Pathway for Colon Cancer Interception

The role of chronic inflammation and arachidonic acid (AA) metabolism in tumor progression has been well characterized for variety of cancers, with compelling data for colon cancer. Several preclinical and clinical studies primarily focused on inhibiting the cyclooxygenase pathways using NSAIDs and aspirin for colon cancer prevention. However, emerging evidence clearly supports the pro-tumorigenic role of 5-lipoxygenase and its downstream leukotriene pathway within AA metabolism. As discussed in the current issue, targeting the leukotriene pathway by cysteinyl leukotriene receptor antagonist (LTRA) montelukast suppressed formation of aberrant crypt foci (ACF) and cell proliferation in colonic epithelium, suggesting the potential of LTRAs for colon cancer prevention. Although this is a short clinical chemoprevention trial to explore the effects of LTRAs against ACF development, it is a significant and timely study opening avenues to further explore the possibilities of using LTRAs in other inflammation-associated precancerous lesions as well. In this spotlight commentary, we highlight the implications of their data and the opportunities for developing LTRAs as potential candidates for colorectal cancer interception. See related article by Higurashi et al., p. 661.