KEGG   PATHWAY: hsa01522Help
Entry
hsa01522                    Pathway                                

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: antineoplastic
BRITE hierarchy
Pathway map
hsa01522  Endocrine resistance
hsa01522

Ortholog table
Disease
H02061  Estrogen resistance syndrome
Drug
D03793  Ilomastat (USAN/INN)
D03795  Marimastat (USAN/INN)
D03797  Prinomastat (USAN/INN)
D03802  Tanomastat (USAN/INN)
D07928  Ethinylestradiol propanesulfonate
D11262  Andecaliximab (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
Int J Mol Sci 14:108-45 (2012)
DOI:10.3390/ijms14010108
Reference
  Authors
Musgrove EA, Sutherland RL
  Title
Biological determinants of endocrine resistance in breast cancer.
  Journal
Nat Rev Cancer 9:631-43 (2009)
DOI:10.1038/nrc2713
Reference
  Authors
Giuliano M, Schifp R, Osborne CK, Trivedi MV
  Title
Biological mechanisms and clinical implications of endocrine resistance in breast cancer.
  Journal
Breast 20 Suppl 3:S42-9 (2011)
DOI:10.1016/S0960-9776(11)70293-4
Reference
  Authors
Ma CX, Reinert T, Chmielewska I, Ellis MJ
  Title
Mechanisms of aromatase inhibitor resistance.
  Journal
Nat Rev Cancer 15:261-75 (2015)
DOI:10.1038/nrc3920
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
Oncol Rep 32:3-15 (2014)
DOI:10.3892/or.2014.3190
Reference
  Authors
Luqmani YA, Alam-Eldin N
  Title
Overcoming Resistance to Endocrine Therapy in Breast Cancer: New Approaches to a Nagging Problem.
  Journal
Med Princ Pract 25 Suppl 2:28-40 (2016)
DOI:10.1159/000444451
Reference
  Authors
Bianco S, Gevry N
  Title
Endocrine resistance in breast cancer: from cellular signaling pathways to epigenetic mechanisms.
  Journal
Transcription 3:165-70 (2012)
DOI:10.4161/trns.20496
Reference
  Authors
Osborne CK, Schiff R
  Title
Mechanisms of endocrine resistance in breast cancer.
  Journal
Annu Rev Med 62:233-47 (2011)
DOI:10.1146/annurev-med-070909-182917
Reference
  Authors
Miller TW
  Title
Endocrine resistance: what do we know?
  Journal
Am Soc Clin Oncol Educ Book 0011300037 (2013)
DOI:10.1200/EdBook_AM.2013.33.e37
Reference
  Authors
Lonning PE, Eikesdal HP
  Title
Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved.
  Journal
Endocr Relat Cancer 20:R183-201 (2013)
DOI:10.1530/ERC-13-0099
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
Int J Mol Sci 16:24243-75 (2015)
DOI:10.3390/ijms161024243
Reference
  Authors
Chang M
  Title
Tamoxifen resistance in breast cancer.
  Journal
Biomol Ther (Seoul) 20:256-67 (2012)
DOI:10.4062/biomolther.2012.20.3.256
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
Biochim Biophys Acta 1795:62-81 (2009)
DOI:10.1016/j.bbcan.2008.08.003
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
Breast Cancer Res 15:R114 (2013)
DOI:10.1186/bcr3581
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
Breast Care (Basel) 8:248-55 (2013)
DOI:10.1159/000354757
Reference
  Authors
Ring A, Dowsett M
  Title
Mechanisms of tamoxifen resistance.
  Journal
Endocr Relat Cancer 11:643-58 (2004)
DOI:10.1677/erc.1.00776
Reference
  Authors
Ribeiro JR, Freiman RN
  Title
Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer.
  Journal
J Steroid Biochem Mol Biol 143:160-73 (2014)
DOI:10.1016/j.jsbmb.2014.02.010
Reference
  Authors
Wang D, Hu L, Zhang G, Zhang L, Chen C
  Title
G protein-coupled receptor 30 in tumor development.
  Journal
Endocrine 38:29-37 (2010)
DOI:10.1007/s12020-010-9363-z
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
Nat Rev Clin Oncol 12:573-83 (2015)
DOI:10.1038/nrclinonc.2015.117
KO pathway
ko01522   

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