Medullary thyroid cancer accounts for about of thyroid malignancies in the USA in 2012. Though two kinase inhibitors vandetanib and cabozantinib improve progressionfree survival of MTC and were approved by FDA recently, no curable therapies are available for metastatic MTC. Overall, the mortality from thyroid cancer has been slightly increasing yearly since 1992. Novel therapies are needed to improve the outcomes of patients with refractory thyroid cancer. Histone deacetylases remove acetyl groups from lysine residues in histone and non-histone substrates, including order SHP099 transcription factors and proteins controlling cell cycle, proliferation and apoptosis. HDACs are divided into 4 classes according to their homology to their yeast orthologues and as appear to be promising targets for cancer therapy. Inhibition of HDACs using small molecules induces multiple biologic effects, including ROS accumulation, cell cycle arrest, DNA damage and apoptosis that can lead to cytotoxic effects. Malignant cells are considered to be more prone to HDAC inhibitors than benign cells. FDA has approved two HDAC inhibitors suberoylanilide hydroxamic acid and depsipeptide in the treatment of cutaneous T cell lymphoma. In thyroid samples, ATC has highest proportion of HDAC1 and 2 overexpression, followed by papillary cancer and normal thyroid tissue, suggesting HADC1 and 2 contribute to thyroid cancer tumorigenesis and dedifferentiation. In line with these findings, Na+/I-symporter expression and iodine accumulation could be AZD5363 induced by HDAC inhibitors in poorly differentiated and undifferentiated thyroid cancer. In addition to promoting cell re-differentiation, HDAC inhibitors are able to induce apoptosis in thyroid cancer. These findings suggest that HDAC inhibitors have the potential to treat thyroid cancer through inducing cancer cell re-differentiation and apoptosis. Furthermore, combination therapy of HDAC inhibitor with chemotherapy may enhance therapeutic efficacy against ATC. Therefore, HDAC inhibitors are potential agents in the treatment of patients with refractory thyroid cancer. PXD101 is a pan-HDAC inhibitor with potent cytotoxic effects against a var
