Targeting IL-8 in colorectal cancer

Introduction: Colorectal cancer is the leading cause of death from gastrointestinal malignancy in the US. Chemokines and their receptors are being recognized as key regulators of cancers and increasingly as therapeutic targets for metastatic cancers, including colorectal cancer. Several studies have demonstrated that IL-8 and its receptor CXCR2 are two of the most significantly upregulated chemokines in colorectal cancer. IL-8 through binding to its receptors can act not only on inflammatory responses and infectious diseases, but also on cancer cells via their receptors to promote migration, invasion and proliferation, and in vivo angiogenesis. Therefore, IL-8 and CXCR2 may be important therapeutic targets against colorectal cancer. Areas covered: This review provides an update on the roles of IL-8 and its receptors in colorectal cancer preclinical models and translational relevance: i) Increased expression of IL-8 and/or its receptors has been characterized in colon cancer cells; ii) IL-8 signaling pathway in colorectal cancer cells; iii) targeting IL-8 expression, or receptor-targeted strategies in colorectal cancer, eliminates the redundant function of IL-8 signaling and determines the effects of suppressing IL-8 signaling on tumor progression and development. Expert opinion: IL-8 and its receptor CXCR2 may function as significant regulatory factors within the tumor microenvironment and be important therapeutic targets in colorectal cancers. Not only may they lead to antitumor properties, but also they may chemosensitize the tumor toward the current chemotherapy.