A novel first-in-class small molecule (ERX-11) that interacts with and disrupts the interactome of the estrogen receptor (ER), blocks the growth of ER-positive breast cancers, including those that are resistant to currently approved hormonal agents.
Two common mutant versions of estrogen receptor alpha achieve constitutive activity and hormone-resistance by preferentially adopting a suite of conformations that expose the coregulator-binding surface.
Activation of the Estrogen Receptor by estra-2-diol results in sustained binding and the previously described cyclical response kinetics are likely an artefact of observing a highly variable process without replicates.
Anti-inflammatory effects of resveratrol are mediated by the estrogen receptor to coordinate a complex array of transcriptional coregulators, suggesting that estrogenic effects must be considered in the complex polypharmacology of resveratrol.
GDC-0810 is a novel, orally bioavailable SERD that exhibits robust pre-clinical activity in models of ER+ breast cancer, including models of tamoxifen resistance, and those that express the ERα mutations, ER.Y537S and ER.D538G.
Driving melanoma differentiation through G protein-coupled estrogen receptor signaling decreases proliferative capacity, decreases expression of the oncodriver and stem cell marker c-Myc, and increases the effectiveness of immunotherapy.
Loss of RUNX1, a key regulator of estrogen receptor-positive luminal breast cells, impairs mammary epithelial differentiation and contributes to luminal breast cancer via genetic interactions with a loss of p53 or RB1.