Entry Name Endocrine resistance - Homo sapiens (human)
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.
Class Human Diseases; Drug resistance: antineoplasticBRITE hierarchy
Pathway map Ortholog table Drug D07928 Ethinylestradiol propanesulfonate
D11262 Andecaliximab (USAN/INN)
D12628 Vepdegestrant (JAN/USAN/INN)
D12827 Palazestrant (USAN/INN)
Organism Homo sapiens (human) [GN:
hsa ]
Reference Authors Garcia-Becerra R, Santos N, Diaz L, Camacho J
Title Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance.
Journal Reference Authors Musgrove EA, Sutherland RL
Title Biological determinants of endocrine resistance in breast cancer.
Journal Reference Authors Giuliano M, Schifp R, Osborne CK, Trivedi MV
Title Biological mechanisms and clinical implications of endocrine resistance in breast cancer.
Journal Reference Authors Ma CX, Reinert T, Chmielewska I, Ellis MJ
Title Mechanisms of aromatase inhibitor resistance.
Journal Reference Authors Viedma-Rodriguez R, Baiza-Gutman L, Salamanca-Gomez F, Diaz-Zaragoza M, Martinez-Hernandez G, Ruiz Esparza-Garrido R, Velazquez-Flores MA, Arenas-Aranda D
Title Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review).
Journal Reference Authors Luqmani YA, Alam-Eldin N
Title Overcoming Resistance to Endocrine Therapy in Breast Cancer: New Approaches to a Nagging Problem.
Journal Reference Authors Bianco S, Gevry N
Title Endocrine resistance in breast cancer: from cellular signaling pathways to epigenetic mechanisms.
Journal Reference Authors Osborne CK, Schiff R
Title Mechanisms of endocrine resistance in breast cancer.
Journal Reference Authors Miller TW
Title Endocrine resistance: what do we know?
Journal Reference Authors Lonning PE, Eikesdal HP
Title Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved.
Journal Reference Authors Egeland NG, Lunde S, Jonsdottir K, Lende TH, Cronin-Fenton D, Gilje B, Janssen EA, Soiland H
Title The Role of MicroRNAs as Predictors of Response to Tamoxifen Treatment in Breast Cancer Patients.
Journal Reference Authors Chang M
Title Tamoxifen resistance in breast cancer.
Journal Reference Authors Zilli M, Grassadonia A, Tinari N, Di Giacobbe A, Gildetti S, Giampietro J, Natoli C, Iacobelli S
Title Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer.
Journal Reference Authors Mo Z, Liu M, Yang F, Luo H, Li Z, Tu G, Yang G
Title GPR30 as an initiator of tamoxifen resistance in hormone-dependent breast cancer.
Journal Reference Authors Hasson SP, Rubinek T, Ryvo L, Wolf I
Title Endocrine resistance in breast cancer: focus on the phosphatidylinositol 3-kinase/akt/mammalian target of rapamycin signaling pathway.
Journal Reference Authors Ring A, Dowsett M
Title Mechanisms of tamoxifen resistance.
Journal Reference Authors Ribeiro JR, Freiman RN
Title Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer.
Journal Reference Authors Wang D, Hu L, Zhang G, Zhang L, Chen C
Title G protein-coupled receptor 30 in tumor development.
Journal Reference Authors Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R
Title ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer.
Journal Related hsa00982 Drug metabolism - cytochrome P450
KO pathway
