scholarly journals Simvastatin functions as a heat shock protein 90 inhibitor against triple-negative breast cancer

2018 ◽  
Vol 109 (10) ◽  
pp. 3272-3284 ◽  
Author(s):  
Xinhui Kou ◽  
Xiaoxiao Jiang ◽  
Huijuan Liu ◽  
Xuan Wang ◽  
Fanghui Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Heat Shock Protein 90

Phase Ib study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple-negative breast cancer (NCT02474173).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1127-TPS1127
Author(s):  
Robert Wesolowski ◽  
Maryam B. Lustberg ◽  
Raquel E. Reinbolt ◽  
Jeffrey Bryan VanDeusen ◽  
Sagar D. Sardesai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Standard Dose ◽  
Heat Shock Protein 90 ◽  
Mapk Signaling ◽  
Amino Terminal ◽  
Client Proteins

TPS1127 Background: Heat shock protein 90 (HSP90) is a molecular chaperone which is necessary for proper folding and stabilization of proteins. Client proteins of HSP90 include many oncogenic proteins known to be over-activated in triple negative breast cancer such as AKT, EGFR, members of RAS/MAPK signaling pathway and androgen receptor. High expression of HSP90 in breast cancer has been associated with poor outcome. In addition, over-expression of HSP90 client proteins such as AKT and c-RAF has been implicated in paclitaxel resistance. Onalespib (AT13387) is a synthetic non-ansamycin small molecule that acts as an inhibitor of HSP90 by binding to the amino terminal of the protein and has dissociation constant (Kd) of 0.71 nM. Methods: Patients with inoperable or metastatic, triple negative or < 10% hormone receptor positive breast cancer are treated with onalespib and paclitaxel on days 1, 8, 15 every 28 days. Paclitaxel is given at a standard dose of 80 mg/m2 while the dose of onalespib is gradually increased using standard 3+3 design (see table). In order to assess the effect of each drug on pharmacokinetics of the other drug, onalespib is given on day -7 prior to cycle 1 and skipped on day 1 of cycle 1 during which paclitaxel is administered alone. The primary objective of the study is to determine recommended phase II dose and assess the toxicity profile of the combination. The secondary objectives include pharmacokinetic of each agent. Overall response rate, response duration and progression-free survival will also be assessed. The study is currently enrolling patients to dose level 2. Clinical trial information: NCT02474173. [Table: see text]

Design, Synthesis, and Evaluation of Heat Shock Protein 90 Inhibitors in Human Breast Cancer and Its Metastasis

2016 ◽  
Vol 17 (14) ◽  
pp. 1231-1245 ◽  
Author(s):  
Mehmet Gümus ◽  
Aykut Ozgur ◽  
Lutfi Tutar ◽  
Ali Disli ◽  
Irfan Koca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Human Breast Cancer ◽  
Heat Shock Protein 90 ◽  
Human Breast ◽  
Design Synthesis
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