Investigational histone deacetylase inhibitors for non-Hodgkin lymphomas.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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-XL antagonists and proteasome inhibitors. Future studies should seek to identify biomarkers that predict patient responses to HDIs.
Watanabe
Takashi
T
National Cancer Center Hospital, Hematology Division, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. takawata@ncc.go.jp
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D056572:Histone Deacetylase Inhibitors