Histone acetylation and deacetylation play important roles in the regulation of gene transcription and in the modulation of
chromatin structure. The levels of
histone acetylation are determined by the activities of
histone acetyltransferases and
histone deacetylases (HDACs). HDACs are associated with a number of oncogenes and tumor suppressor genes and can be aberrantly expressed and/or inappropriately activated in
cancer cells.
HDAC inhibitors have therefore recently emerged as a novel treatment modality against
malignancies. They regulate gene expression by enhancing the acetylation of not only
histones but also nonhistone
proteins, including
transcription factors, transcription regulators, signal transduction mediators, and
DNA repair enzymes, and they inhibit
cancer growth.
Vorinostat (
suberoylanilide hydroxamic acid) is one of the most potent
HDAC inhibitors, and was approved in Japan in 2011 for the treatment of
cutaneous T-cell lymphoma. Numerous clinical trials have shown it to be effective against
cutaneous T-cell lymphoma but less so against other types of
cancer. Because
vorinostat can overcome resistance to or enhance the efficacy of other
anticancer agents, such as
5-fluorouracil,
carboplatin,
paclitaxel,
bortezomib, and
tamoxifen, combination
therapies using
vorinostat and these agents have been investigated. This review introduces the background and mechanism of action of
vorinostat and describes the results of clinical trials using
vorinostat, both as a single agent and in combination with other
anticancer agents, against
cutaneous T-cell lymphoma and other
malignancies.