title: HSP90 inhibitor AUY922 can reverse Fulvestrant induced feedback reaction in human breast cancer cells.
abstract: Hormone therapy has become one of the main strategies for breast cancer, however, many estrogen receptor (ER) positive patients end in tumor collapse due to initial or acquired resistance to hormone treatment, which includes Fulvestrant. Here we report that ErbB receptors and downstream PI3K/AKT and ERK pathway have been reactivated after treatment of Fulvestrant in ER positive MCF-7 and T47D cells, which are related to Fulvestrant resistance. HSP90 is a universally expressed chaperone protein and plays a vital role in both normal and cancer cells, HSP90 inhibitor AUY922 can reverse this feedback reactivation effect of Fulvestrant by targeting multiple proteins related in ErbB receptors, PI3K/AKT and ERK pathway, which is much better than single targeting inhibitors. We also consolidate these effects in human fresh breast tumors. Combination of AUY922 and Fulvestrant may become a promising therapy strategy in breast cancer treatment.
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Jingchao
authors.identifier: http://orcid.org/0000-0001-8228-9730
authors.initials: J
authors.lastname: Bai
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.|Department of Lymphoma, Tianjin Medical university Cancer Hospital, Sino-US Center for Lymphoma and Leukemia, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Third Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.|Tianjin's Clinical Research Center for Cancer, Tianjin, China.|Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D061986:MCF-7 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C528044:5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; D018931:Antineoplastic Agents, Hormonal; D018841:HSP90 Heat-Shock Proteins; D007555:Isoxazoles; D011960:Receptors, Estrogen; D012118:Resorcinols; D000077267:Fulvestrant; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: AUY922; ErbB receptors; PI3K/AKT; fulvestrant; hormone resistance