Bortezomib-induced Epstein-Barr virus and Kaposi sarcoma herpesvirus lytic gene expression: oncolytic strategies

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.