[OA] Antiestrogens: Structure Activity Relationships and Use in Breast Cancer Treatment
About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs.
The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action.
AEs are typically classified as Selective Estrogen Receptor Modulators (SERMs), which display tissue-specific partial agonist activity (e.g. tamoxifen and raloxifene), or as pure AEs (e.g. fulvestrant), which enhance ERα post-translational modification by ubiquitin-like molecules and accelerate its proteasomal degradation.
Characterization of second and third generation AEs however suggests induction of diverse ERα structural conformations, resulting in variable degrees of receptor down-regulation and different patterns of systemic properties in animal models and in the clinic.
Traboulsi T, El Ezzy M, Gleason J, Mader S. Antiestrogens: structure activity relationships and use in breast cancer treatment. Journal of Molecular Endocrinology. http://jme.endocrinology-journals.org/content/early/2016/10/11/JME-16-0024.abstract
About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs.
The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action.
AEs are typically classified as Selective Estrogen Receptor Modulators (SERMs), which display tissue-specific partial agonist activity (e.g. tamoxifen and raloxifene), or as pure AEs (e.g. fulvestrant), which enhance ERα post-translational modification by ubiquitin-like molecules and accelerate its proteasomal degradation.
Characterization of second and third generation AEs however suggests induction of diverse ERα structural conformations, resulting in variable degrees of receptor down-regulation and different patterns of systemic properties in animal models and in the clinic.
Traboulsi T, El Ezzy M, Gleason J, Mader S. Antiestrogens: structure activity relationships and use in breast cancer treatment. Journal of Molecular Endocrinology. http://jme.endocrinology-journals.org/content/early/2016/10/11/JME-16-0024.abstract
