Investigational histone deacetylase inhibitors for non-Hodgkin lymphomas

Abstract

Importance of the field: Histone deacetylase inhibitors (HDIs) have been shown effective as single agents for cutaneous T-cell lymphomas, peripheral T-cell lymphomas, and B-cell lymphomas, such as follicular lymphoma and mantle cell lymphoma. Of interest, HDIs in combination with other drugs can be a treatment for Epstein–Barr virus-associated lymphoproliferative disorders. Our data of gene expression profiles in PBMCs of responders to vorinostat was discussed.

Areas covered in this review: This review summarizes recent clinical trials of HDIs in non-Hodgkin lymphomas, the effects of HDIs in in vitro and mouse models, and the possibility of future combination treatments.

What the reader will gain: The HDI dosing schedule is crucial to optimize outcomes and avoid irreversible adverse effects. Responses to HDIs are slow, highlighting the need to continue treatment until the maximum response is achieved. HDIs cause hyperacetylation of histone and nonhistone proteins, resulting in various effects on neoplastic cells and immune responses in their microenvironment.

Take home message: Even though HDIs are not potent as single agents, they are likely to provide promising therapeutic options when combined with other agents, i.e., BCL2/BCL-X_L antagonists and proteasome inhibitors. Future studies should seek to identify biomarkers that predict patient responses to HDIs.

Keywords::

• belinostat
• depsipeptide
• HDI
• histone deacetylase inhibitor
• NHL
• non-Hodgkin lymphoma
• panobinostat
• romidepsin
• SAHA
• suberoylanilide hydroxamic acid
• vorinostat

Acknowledgements

The author is grateful to Ms T Yamano, a clinical research coordinator of the National Cancer Center Hospital, who collected the data of a Phase I trial of vorinostat for Japanese patients with malignant lymphoma.

Notes

This box summarizes key points contained in the article.