In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-07-13)
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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.15828.001
DOI:
10.7554/eLife.15828.002
DOI:
10.7554/eLife.15828.003
DOI:
10.7554/eLife.15828.004
DOI:
10.7554/eLife.15828.005
DOI:
10.7554/eLife.15828.006
DOI:
10.7554/eLife.15828.007
DOI:
10.7554/eLife.15828.008
DOI:
10.7554/eLife.15828.009
DOI:
10.7554/eLife.15828.010
DOI:
10.7554/eLife.15828.011
DOI:
10.7554/eLife.15828.012
DOI:
10.7554/eLife.15828.013
DOI:
10.7554/eLife.15828.014
DOI:
10.7554/eLife.15828.015
DOI:
10.7554/eLife.15828.016
DOI:
10.7554/eLife.15828.017
DOI:
10.7554/eLife.15828.018
DOI:
10.7554/eLife.15828.019
DOI:
10.7554/eLife.15828.021
DOI:
10.7554/eLife.15828.022
DOI:
10.7554/eLife.15828.023
DOI:
10.7554/eLife.15828.020
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
