Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas

HSP90, a highly conserved molecular chaperone that regulates the function of several oncogenic client proteins, is altered in glioblastoma. However, HSP90 inhibitors currently in clinical trials are short-acting, have unacceptable toxicities, or are unable to cross the blood-brain barrier (BBB). We...

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Veröffentlicht in:	Clinical cancer research 2017-10, Vol.23 (20), p.6215-6226
Hauptverfasser:	Canella, Alessandro, Welker, Alessandra M, Yoo, Ji Young, Xu, Jihong, Abas, Fazly S, Kesanakurti, Divya, Nagarajan, Prabakaran, Beattie, Christine E, Sulman, Erik P, Liu, Joseph, Gumin, Joy, Lang, Frederick F, Gurcan, Metin N, Kaur, Balveen, Sampath, Deepa, Puduvalli, Vinay K
Format:	Artikel
Sprache:	eng
Schlagworte:	AKT protein Angiogenesis Animal models Animals Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Benzamides - pharmacokinetics Benzamides - pharmacology Biological effects Biotechnology Blood-brain barrier Blood-Brain Barrier - metabolism Brain Brain tumors Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Cell survival Chemical compounds Clinical trials Dacarbazine - analogs & derivatives Dacarbazine - pharmacokinetics Dacarbazine - pharmacology Danio rerio Disease Models, Animal Drug Synergism Drug Therapy, Combination Effectiveness Epidermal growth factor receptors ErbB Receptors - metabolism Experimental design Extracellular Signal-Regulated MAP Kinases - metabolism Female Gene Expression Glioblastoma Glioma - drug therapy Glioma - metabolism Glioma - mortality Glioma - pathology Glioma cells HSP90 Heat-Shock Proteins - antagonists & inhibitors HSP90 Heat-Shock Proteins - genetics HSP90 Heat-Shock Proteins - metabolism Hsp90 protein Humans Inhibitors Isoindoles - pharmacokinetics Isoindoles - pharmacology Medical research Mice Neoplastic Stem Cells - metabolism Pharmacokinetics Pharmacology Protein Transport Proteins Proto-Oncogene Proteins c-akt - metabolism Ribosomal Protein S6 Kinases - metabolism Signal Transduction - drug effects Signaling Survival Survival Rate Temozolomide Toxicity Xenograft Model Antitumor Assays Xenografts Zebrafish
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