Targeting toll-like receptors in cancer prevention

There is a pressing need for the development of new prevention strategies for the most common worldwide malignancy, nonmelanoma skin cancer (NMSC), as sun protection efforts have not proven to be completely effective. Interestingly, despite the known circumstance that individuals undergoing chronic immunosuppression are at a substantially increased risk for developing NMSC, in this issue of Cancer Prevention Research, Blohm-Mangone and colleagues provide new evidence that topical application of the Toll-like receptor 4 (TLR4) antagonist resatorvid may be efficacious as a chemopreventive agent in NMSC specifically via blocking UV-induced inflammatory signaling. These new findings highlight a potentially delicate dichotomy between the role of innate immune receptors in the normal, protective immunosurveillance of damaged cells in the skin and the pathogenic UV-induced overstimulation of cutaneous inflammation that promotes photocarcinogenesis. Given the tremendous cancer burden incurred by NMSC, further exploration of the use of TLR4 antagonists in NMSC chemoprevention strategies is certainly warranted.