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

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Gamma herpesviruses (GHVs) are linked to numerous human cancers, especially in immunocompromised patients.
• Targeting latent viruses within tumors via lytic activation presents a novel antineoplastic therapeutic approach.

Purpose of the Study:

• To review the potential of proteasome inhibitors as a strategy for activating gamma herpesviruses (GHVs) for cancer therapy.
• To explore the mechanisms and clinical relevance of bortezomib in treating GHV-related malignancies.

Main Methods:

• Review of existing literature on proteasome inhibitors and their effect on gamma herpesvirus (GHV) lytic cycles.
• Analysis of case reports and mechanistic studies investigating bortezomib's activity against GHV-related cancers.

Main Results:

• Bortezomib, a proteasome inhibitor, effectively induces the lytic cycle of gamma herpesviruses (GHVs).
• Case reports show bortezomib has activity against GHV-related malignancies.
• While NF-κB pathway inhibition was initially suspected, alternative pathways mediate bortezomib's lytic induction and anti-cancer effects.

Conclusions:

• Proteasome inhibition is a promising oncolytic strategy warranting further investigation.
• Clinical trials are essential to correlate GHV lytic induction with bortezomib response.
• Optimization of this oncolytic strategy requires understanding its clinical efficacy and mechanisms.