Elevated expression of CUEDC2 protein confers endocrine resistance in breast cancer

Downregulation of estrogen receptor-α (ER-α) in breast tumors can mediate resistance to ER-α–targeted therapies such as tamoxifen. This report sheds light on a therapy resistance–conferring adaptation by identifying a new regulator of ER-α stability. CUE domain–containing protein-2 (CUEDC2) can bind to and promote degradation of ER-α, thereby driving tamoxifen resistance. Elevated CUEDC2 elevation in human breast cancers correlates with attenuated prognosis after tamoxifen treatment, thus suggesting its potential as a clinical predictor.