Activation of the estrogen receptor alpha (ERα) is of prime importance for the development of hormone-dependent breast cancers. Hence, drugs able to impede the emergence of an active folding of ERα have been used for a long time as a first line therapeutic strategy. Aromatase inhibitors that block estradiol synthesis and / or antiestrogens that compete with hormone binding to the receptor are routinely prescribed. Unfortunately, emergence of tumor resistance almost invariably results from currently used antihormonal approaches. One may anticipate that a “multi-target” strategy affecting key regulatory domains distinct from ligand binding pocket of ERα may help to circumvent this problem. To reach this goal, the synthesis of peptides that may specifically inhibit intra- or inter-molecular interactions has been proposed. This paper describes functional motifs potentially suitable for the design of such antagonists. Activity of available peptidic and non-peptidic mimics of these motifs is also reviewed.
Keywords: Breast cancer, Estrogen Receptor alpha, coregulator, platform motif, peptide, LxxLL, signal transduction, site-directed mutagenesis, detoxifying enzymes, Alpha-fetoprotein (AFP), Human ES cell-derived dopaminergic neurons, cell therapy in neurodegenerative diseases, neural stem cells in Parkinson, ’, s disease, Gene therapy, Regeneration-based therapies, embryonic germ cells, epigenetic reprogramming, Stem Cell Research, stem cell-specific expertise, human embryonic pluripotent stem cells, adult stem cells, stem cell-based therapies, progenitor cell transplants, Transplanted dopaminergic
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