The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer.

ABSTRACT: ER-targeted therapeutics provide valuable treatment options for patients with ER+ breast cancer, however, current relapse and mortality rates emphasize the need for improved therapeutic strategies. The recent discovery of prevalent ESR1 mutations in relapsed tumors underscores a sustained reliance of advanced tumors on ER? signaling, and provides a strong rationale for continued targeting of ER?. Here we describe GDC-0810, a novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was identified by prospectively optimizing ER? degradation, antagonism and pharmacokinetic properties. GDC-0810 induces a distinct ER? conformation, relative to that induced by currently approved therapeutics, suggesting a unique mechanism of action. GDC-0810 has robust in vitro and in vivo activity against a variety of human breast cancer cell lines and patient derived xenografts, including a tamoxifen-resistant model and those that harbor ER? mutations. GDC-0810 is currently being evaluated in Phase II clinical studies in women with ER+ breast cancer.

SUBMITTER: Joseph JD 

PROVIDER: S-EPMC4961458 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature