HSP90 inhibitor AUY922 can reverse Fulvestrant induced feedback reaction in human breast cancer cells

被引：12

作者：

Bai, Jingchao ^{[1
,2
,3
]}

Zhou, Guanglin ^{[1
,2
,3
]}

Qiu, Yufan ^{[1
,2
,3
]}

Hu, Yunhui ^{[1
,2
,3
]}

Liu, Jingjing ^{[1
,2
,3
]}

Zhao, Jing ^{[1
,2
,3
,4
]}

Zhang, Sheng ^{[1
,2
,3
]}

Zhang, Jin ^{[1
,2
,3
]}

机构：

[1] Tianjin Med Univ Canc Inst & Hosp, Dept Breast Canc 3, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China

[2] Tianjins Clin Res Ctr Canc, Tianjin, Peoples R China

[3] Tianjin Med Univ, Key Lab Breast Canc Prevent & Therapy, Minist Educ, Tianjin, Peoples R China

[4] Tianjin Med Univ Canc Hosp, Dept Lymphoma, Sino US Ctr Lymphoma & Leukemia, Tianjin Key Lab Canc Prevent & Therapy, Tianjin, Peoples R China

来源：

CANCER SCIENCE | 2017年 / 108卷 / 06期

关键词：

AUY922; ErbB receptors; fulvestrant; hormone resistance; PI3K; AKT; PROTEIN; 90; INHIBITOR; LUNG-CANCER; PHASE-II; ACQUIRED-RESISTANCE; POTENT ACTIVITY; GANETESPIB; TAMOXIFEN; THERAPY; KINASE; GROWTH;

D O I：

10.1111/cas.13238

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

收藏

页码：1177 / 1184

页数：8

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