The HSP90 inhibitor NVP-AUY922 inhibits growth of HER2 positive and trastuzumab-resistant breast cancer cells

被引：21

作者：

Canonici, Alexandra ^{[1
]}

Qadir, Zulfiqar ^{[1
]}

Conlon, Neil T. ^{[1
]}

Collins, Denis M. ^{[1
]}

O'Brien, Neil A. ^{[2
]}

Walsh, Naomi ^{[1
]}

Eustace, Alex J. ^{[1
]}

O'Donovan, Norma ^{[1
]}

Crown, John ^{[1
,3
]}

机构：

[1] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA

[3] St Vincents Univ Hosp, Dept Med Oncol, Dublin, Ireland

来源：

INVESTIGATIONAL NEW DRUGS | 2018年 / 36卷 / 04期

基金：

爱尔兰科学基金会;

关键词：

Hsp90 (heat shock protein 90); AUY922; Trastuzumab; ErbB2; CHAPERONE MACHINERY; TUMOR-GROWTH; CHEMOTHERAPY; COMBINATION; HERCEPTIN; LAPATINIB; MODELS; KINASE; CONTRIBUTES;

D O I：

10.1007/s10637-017-0556-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

As HER2 is a client protein of the molecular chaperone Hsp90, targeting Hsp90 may be beneficial in HER2-positive breast cancer. In this study, the activity of the Hsp90 inhibitor NVP-AUY922 was assessed in HER2 overexpressing breast cancer cell lines, including two cell line models of acquired trastuzumab-resistance. The seven HER2-positive breast cancer cell lines tested showed significant sensitivity to NVP-AUY922 in vitro, with IC50 values between 6 and 17 nM. Combining NVP-AUY922 with chemotherapy did not improve response. NVP-AUY922 in combination with trastuzumab, significantly enhanced growth inhibition in three of the seven cell lines tested. In conclusion, our data shows that NVP-AUY922 displays potent anti-cancer activity in HER2-positive and trastuzumab-resistant breast cancer cells, and supports further testing of NVP-AUY922 in patients with HER2-positive breast cancer.

引用

页码：581 / 589

页数：9

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