The turnover of estrogen receptor α by the selective estrogen receptor degrader (SERD) fulvestrant is a saturable process that is not required for antagonist efficacy.

ABSTRACT: It has become apparent of late that even in tamoxifen and/or aromatase resistant breast cancers, ERα remains a bona fide therapeutic target. Not surprisingly, therefore, there has been considerable interest in developing Selective ER Degraders (SERDs), compounds that target the receptor for degradation. Currently, ICI 182,780 (ICI, fulvestrant) is the only SERD approved for the treatment of breast cancer. However, the poor pharmaceutical properties of this injectable drug and its lack of superiority over second line aromatase inhibitors in late stage breast cancer have negatively impacted its clinical use. These findings have provided the impetus to develop second generation, orally bioavailable SERDs with which quantitative turnover of ERα in tumors can be achieved. Interestingly however,

SUBMITTER: Wardell SE 

PROVIDER: S-EPMC3109090 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature