Antiestrogens are useful in the treatment of endocrine-respon sive breast cancers in humans. In an attempt to understand the mechanisms underlying their estrogen antagonism and antitumor character, we have examined the interaction of antiestrogens with three human breast cancer cell lines that differ markedly in their estrogen receptor content and in their sensitivity to growth suppression by a...

This paper reviews actions of antiestrogens on IGF physiology, and discusses the potential significance of the recent observations that (i) effects of antiestrogens on the uterus are correlated with their effects on uterine IGF-I and IGFBP-3 gene expression, and that (ii) the potent antiestrogen and growth inhibitor ICI 182,780 induces autocrine production of IGFBP-3 by estrogen receptor-positi...

An AKT inhibitor plus an antiestrogen exhibited no significant clinical activity in patients with ER(+)/HER2(-) breast cancer despite laboratory studies supporting an antitumor effect for both drugs combined. These results raise concerns about the development of AKT inhibitors in unselected patients whose tumors have unknown dependence on the PI3K/AKT pathway. Clin Cancer Res; 22(11); 2599-601....

We report the synthesis of 7alpha-substituted beta-estradiol derivatives bearing side chains terminated with cholesterol and 3beta-cholesterylamine. These chimeric compounds were designed to exhibit high affinity for estrogen receptors (ERs) and cellular plasma membranes to potentially enable regulated uptake of ERs by mammalian cells. Evaluation with recombinant yeast reporting compound-mediat...