Journal
CURRENT OPINION IN ONCOLOGY
Volume 23, Issue 5, Pages 482-487Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCO.0b013e3283499c37
Keywords
bortezomib; Epstein-Barr virus; gamma herpesvirus; human immunodeficiency virus; Kaposi sarcoma herpesvirus; oncolytic
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Funding
- Millennium Pharmaceuticals
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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-kappa B 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.
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