Abstract
Purpose of review:
Gamma herpesviruses (GHVs) are responsible for a substantial proportion of virus-associated human cancers, particularly in immunocompromised individuals. Methods that employ lytic activation of viruses latently infecting tumors represent a novel strategy of antineoplastic therapy.
Recent findings:
The proteasome inhibitor, bortezomib, has been shown to be a potent activator of GHV lytic cycle and has demonstrated activity in case reports of GHV-related malignancies. Although initial reports implicated the inhibition of the NF-κB pathway, more recent studies identify alternative pathways responsible for bortezomib-mediated lytic induction of GHVs and activity against the malignancies that harbor them.
Summary:
Further exploration of proteasome inhibition as an oncolytic strategy is warranted and will require clinical/translational trials to determine whether lytic induction of GHVs correlates with clinical response to bortezomib, and, if so, to optimize this oncolytic strategy.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Boronic Acids / adverse effects
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Boronic Acids / pharmacology
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Boronic Acids / therapeutic use*
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Bortezomib
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Carcinoma / drug therapy
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Carcinoma / epidemiology
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Carcinoma / virology
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Epstein-Barr Virus Infections / complications
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Gene Expression Regulation, Viral / drug effects*
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Herpesvirus 4, Human / drug effects*
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Herpesvirus 4, Human / genetics
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Herpesvirus 4, Human / physiology
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Herpesvirus 8, Human / drug effects*
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Herpesvirus 8, Human / genetics
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Herpesvirus 8, Human / physiology
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Humans
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Incidence
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Lymphoma / drug therapy
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Lymphoma / epidemiology
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Lymphoma / virology
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Proteasome Inhibitors
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Pyrazines / adverse effects
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Pyrazines / pharmacology
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Pyrazines / therapeutic use*
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Sarcoma, Kaposi / drug therapy
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Sarcoma, Kaposi / epidemiology
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Sarcoma, Kaposi / virology
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Virus Latency / drug effects
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Virus Physiological Phenomena / drug effects*
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Virus Physiological Phenomena / genetics
Substances
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Boronic Acids
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Proteasome Inhibitors
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Pyrazines
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Bortezomib