description
Endocrine therapy is a key treatment strategy to control or eradicate hormone-responsive breast cancer. The most commonly used endocrine therapy agents are selective estrogen receptor modulators (SERMs, e.g. tamoxifen), estrogen synthesis inhibitors (e.g. aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane), and selective estrogen receptor down-regulators (SERDs, e.g. fulvestrant). However, resistance to these agents has become a major clinical obstacle. Mechanisms of endocrine resistance include loss of ER-alpha expression, altered expression of coactivators or coregulators that play a critical role in ER-mediated gene transcription, ligand-independent growth factor signaling cascades that activate kinases and ER-phosphorylation, altered availability of active tamoxifen metabolites regulated by drug-metabolizing enzymes, such as CYP2D6, and deregulation of the cell cycle and apoptotic machinery

external resources
NCBI:1404799
KEGG:hsa01522
PUBMED:24415977
PUBMED:23625614
PUBMED:24841429
PUBMED:15613444
PUBMED:23714450
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PUBMED:24565562
PUBMED:26849149
PUBMED:25907219
PUBMED:20887199

genes
ADCY1 , ADCY2 , ADCY3 , ADCY5 , ADCY6 , ADCY7 , ADCY8 , ADCY9 , JAG1 , AKT1 , AKT2 , ARAF , BAD , BAX , CCND1 , BCL2 , BIK , BRAF , CDK4 , CDKN1A , CDKN1B , CDKN2A , CDKN2C , MAPK14 , CYP2D6 , HBEGF , E2F1 , E2F2 , E2F3 , EGFR , ERBB2 , ESR1 , ESR2 , FOS , MTOR , GNAS , GPER1 , GRB2 , HRAS , IGF1 , IGF1R , JAG2 , JUN , KRAS , MDM2 , MMP2 , MMP9 , NOTCH1 , NOTCH2 , NOTCH3 , NOTCH4 , NRAS , PIK3CA , PIK3CB , PIK3CD , PIK3R1 , PIK3R2 , MED1 , PRKACA , PRKACB , PRKACG , MAPK1 , MAPK3 , MAPK8 , MAPK11 , MAPK9 , MAPK10 , MAPK13 , MAP2K1 , MAP2K2 , PTK2 , RAF1 , RB1 , RPS6KB1 , RPS6KB2 , MAPK12 , SHC1 , SOS1 , SOS2 , SP1 , SRC , TP53 , NCOA3 , PIK3R3 , ABCB11 , NCOR1 , AKT3 , CARM1 , DLL3 , SHC2 , DLL1 , SHC3 , DLL4 , ADCY4 , SHC4 ,