Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma.

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Jaime-Ramirez AC, Yu JG, Caserta E, Yoo JY, Zhang J, Lee TJ, Hofmeister C, Lee JH, Kumar B, Pan Q, Kumar P, Baiocchi R, Teknos T, Pichiorri F, Kaur B, Old M

Reolysin and Histone Deacetylase Inhibition in the Treatment of Head and Neck Squamous Cell Carcinoma.

Mol Ther Oncolytics. 2017 May 10;5:87-96. doi: 10.1016/j.omto.2017.05.002. eCollection 2017 Jun 16.

PubMed ID

28812060 [ View in PubMed

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Abstract

Oncolytic viruses (OVs) are emerging as powerful anti-cancer agents and are currently being tested for their safety and efficacy in patients. Reovirus (Reolysin), a naturally occurring non-pathogenic, double-stranded RNA virus, has natural oncolytic activity and is being tested in phase I-III clinical trials in a variety of tumor types. With its recent US Food and Drug Administration (FDA) orphan drug designation for several tumor types, Reolysin is a potential therapeutic agent for various cancers, including head and neck squamous cell carcinomas (HNSCCs), which have a 5-year survival of approximately 55%. Histone deacetylase inhibitors (HDACis) comprise a structurally diverse class of compounds with targeted anti-cancer effects. The first FDA-approved HDACi, vorinostat (suberoylanilide hydroxamic acid [SAHA]), is currently being tested in patients with head and neck cancer. Recent findings indicate that HDAC inhibition in myeloma cells results in the upregulation of the Reolysin entry receptor, junctional adhesion molecule 1 (JAM-1), facilitating reovirus infection and tumor cell killing both in vitro and in vivo. In this study, we tested the anti-tumor efficacy of HDAC inhibitors AR-42 or SAHA in conjunction with Reolysin in HNSCCs. While HDAC inhibition increased JAM-1 and reovirus entry, the impact of this combination therapy was tested on the development of anti-tumor immune responses.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Vorinostat	Histone deacetylase (Protein Group)	Protein group	Humans	Unknown	Inhibitor	Details