1. Ganetespib, an HSP90 inhibitor, kills Epstein–Barr virus (EBV)-infected B and T cells and reduces the percentage of EBV-infected cells in the blood.
- Author
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Shatzer, Amber, Ali, Mir A., Chavez, Mayra, Dowdell, Kennichi, Lee, Min-Jung, Tomita, Yusuke, El-Hariry, Iman, Trepel, Jane B., Proia, David A., and Cohen, Jeffrey I.
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ENZYME inhibitors synthesis , *CHEMICAL synthesis , *EPSTEIN-Barr virus diseases , *B cell lymphoma , *T cells , *T cell receptors , *GENETICS , *PHYSIOLOGY - Abstract
HSP90 inhibitors have been shown to kill Epstein–Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells with ganetespib, an HSP90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed EBV-positive B and T cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV-positive lymphomas and prolonged survival in SCID mice inoculated with one EBV-transformed B-cell line, but not another B-cell line. The former cell line showed lower levels of EBNA-1 after treatment with ganetespibin vitro. Treatment of a patient with T-cell chronic active EBV with ganetespib reduced the percentage of EBV-positive cells in the peripheral blood. These data indicate that HSP90 inhibitors may have a role in the therapy of certain EBV-associated diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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