The selective estrogen receptor downregulator GDC-0810 is efficacious in diverse models of ER+ breast cancer.
Elife
; 52016 07 13.
Article
em En
| MEDLINE
| ID: mdl-27410477
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 ERα signaling, and provides a strong rationale for continued targeting of ERα. Here we describe GDC-0810, a novel, non-steroidal, orally bioavailable selective ER downregulator (SERD), which was identified by prospectively optimizing ERα degradation, antagonism and pharmacokinetic properties. GDC-0810 induces a distinct ERα 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 ERα mutations. GDC-0810 is currently being evaluated in Phase II clinical studies in women with ER+ breast cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptores de Estrogênio
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Cinamatos
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Indazóis
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Antineoplásicos
Tipo de estudo:
Observational_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Elife
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos