TY - JOUR
T1 - Tanespimycin
T2 - The opportunities and challenges of targeting heat shock protein 90
AU - Erlichman, Charles
N1 - Funding Information:
Supported in part by grant NCI # CA69912 N0-CM62205, CA15083.
PY - 2009/6
Y1 - 2009/6
N2 - Background: Heat shock protein 90 (HSP90) is the core of a multi-chaperone complex critical for the folding, trafficking, and stabilization of many client proteins that are involved in tumor cell proliferation, survival, and angiogenesis. Targeting HSP90 results in degradation of these client proteins. Objective: Data supporting the development of tanespimycin, which targets HSP90, are reviewed. Methods: Clinical data available for tanespimycin development are presented. Results: Tanespimycin can be given safely at biologically active doses with mild toxicity such as nausea, vomiting, diarrhea, and fatigue. Although single-agent studies have shown limited activity, combinations of tanespimycin with bortezomib or trastuzumab have suggested promising avenues of further evaluation in multiple myeloma and breast cancer, respectively. Conclusions: Further development of HSP90-targeted strategies include testing of novel chemical structures having better solubility and stability and the potential for oral administration. Targeting of HSP90 in combination with other heat shock proteins, such as HSP70 or HSP27, may be an alternative strategy that warrants further exploration.
AB - Background: Heat shock protein 90 (HSP90) is the core of a multi-chaperone complex critical for the folding, trafficking, and stabilization of many client proteins that are involved in tumor cell proliferation, survival, and angiogenesis. Targeting HSP90 results in degradation of these client proteins. Objective: Data supporting the development of tanespimycin, which targets HSP90, are reviewed. Methods: Clinical data available for tanespimycin development are presented. Results: Tanespimycin can be given safely at biologically active doses with mild toxicity such as nausea, vomiting, diarrhea, and fatigue. Although single-agent studies have shown limited activity, combinations of tanespimycin with bortezomib or trastuzumab have suggested promising avenues of further evaluation in multiple myeloma and breast cancer, respectively. Conclusions: Further development of HSP90-targeted strategies include testing of novel chemical structures having better solubility and stability and the potential for oral administration. Targeting of HSP90 in combination with other heat shock proteins, such as HSP70 or HSP27, may be an alternative strategy that warrants further exploration.
KW - 17-AAG
KW - HSP90
KW - Heat shock protein
KW - Tanespimycin
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U2 - 10.1517/13543780902953699
DO - 10.1517/13543780902953699
M3 - Review article
C2 - 19466875
AN - SCOPUS:67649625171
SN - 1354-3784
VL - 18
SP - 861
EP - 868
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 6
ER -