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

Authors :
Canonici A
Qadir Z
Conlon NT
Collins DM
O'Brien NA
Walsh N
Eustace AJ
O'Donovan N
Crown J
Source :
Investigational new drugs [Invest New Drugs] 2018 Aug; Vol. 36 (4), pp. 581-589. Date of Electronic Publication: 2018 Feb 02.
Publication Year :
2018

Abstract

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 IC <subscript>50</subscript> 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.

Details

Language :
English
ISSN :
1573-0646
Volume :
36
Issue :
4
Database :
MEDLINE
Journal :
Investigational new drugs
Publication Type :
Academic Journal
Accession number :
29396630
Full Text :
https://doi.org/10.1007/s10637-017-0556-7