Targeting histone deacetylase in thyroid cancer.

INTRODUCTION: Epigenetic changes have been detected in thyroid cancer cells, and evidence indicates that they may contribute to altered differentiation and proliferation of these cells. Histone acetylation/deacetylation represents a major mechanism for modulating the expression of genes, including those involved in neoplastic transformation, and drugs that inhibit histone deacetylase (HDAC) activity have displayed promising anti-tumor activity in many pre-clinical studies. AREAS COVERED: We provide a brief overview of the mechanisms underlying histone acetylation-mediated regulation of gene expression and the principal epigenetic alterations detected in thyroid cancer cells. The review then focuses on the results of pre-clinical and clinical studies (some still underway) in which HDAC inhibitors (HDACi) have been used to treat thyroid cancer. EXPERT OPINION: HDACs are a potentially important target for thyroid cancer treatments. Inhibition of HDAC activity has produced encouraging results in terms of reducing proliferation rates and restoring the iodine-uptake capacity in transformed thyrocytes. HDACi, especially when combined with other molecularly targeted drugs, may represent an important option for those tumors that are unresponsive to the currently available treatments.