Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance.

ABSTRACT: Oestrogen receptor-α (ERα), a key driver of breast cancer, normally requires oestrogen for activation. Mutations that constitutively activate ERα without the need for hormone binding are frequently found in endocrine-therapy-resistant breast cancer metastases and are associated with poor patient outcomes. The location of these mutations in the ER ligand-binding domain and their impact on receptor conformation suggest that they subvert distinct mechanisms that normally maintain the low basal state of wild-type ERα in the absence of hormone. Such mutations provide opportunities to probe fundamental issues underlying ligand-mediated control of ERα activity. Instructive contrasts between these ERα mutations and those that arise in the androgen receptor (AR) during anti-androgen treatment of pr

SUBMITTER: Katzenellenbogen JA 

PROVIDER: S-EPMC6252060 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature