Targeting Estrogen Receptor-β for the Prevention of Nonmelanoma Skin Cancer

The potential for targeting estrogen receptor (ER)-beta in various cancer models has been gaining considerable attention in recent years. In this issue of the journal, Chaudhary and colleagues demonstrate markedly decreased ultraviolet B (UVB)-induced skin cancer in a mouse model using a highly specific ER-beta agonist, ERB-041. The mechanisms that underlie this strong inhibitory effect are mediated by inhibition of proinflammatory signaling and epithelial-mesenchymal transition (EMT). The changes in EMT were due in part to modulation of WNT/beta-catenin signaling. Collectively, the results from these studies provide important new insights into the mechanisms by which the ER-beta agonist ERB-041 inhibits UVB-induced skin cancer and opens the door for future studies that could examine combinatorial approaches for UVB-dependent skin cancer chemoprevention. (C) 2014 AACR.