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 BI-78D3 effects against a variety of cancer types through inducing apoptosis, regardless of inheritant resistance of chemotherapy. The combination of PXD101 with docetaxel showed beneficial effects in treating ovarian and prostate cancer cells. Clinically, combined treatment of PXD101, paclitaxel and carboplatin resulted in partial response in patients with solid tumors in a phase I trial. PXD101 in combination with doxorubicin also has favorable results in the treatment of soft tissue sarcoma in a phase I/II trial. These data prompted us to explore the therapeutic efficacy of PXD101 in thyroid cancer. We also assessed the combination effects of PXD101 and chemotherapy in treating ATC, the most aggressive type of thyroid cancer. HDAC inhibitors are able to promote double-stranded DNA breaks and lead to apoptosis. This mechanism may contribute to cytotoxicity of PXD101 in thyroid cancer. We evaluated the expression of proteins associated with DNA damage and repair in cells treated with PXD101 for 48 hours. p-H2AX, a traditional DSBs marker was significantly enhanced with a dose-dependent manner in all cell lines, supporting PXD101 can induce DSBs in thyroid cancer cells. Prior reports shows HDAC inhibitors can repress DNA repair proteins that contributes to DSBs. We studied this possibility and found PXD101 considerably decreased a Naringin non-homologous end joining DNA repair protein KU70 in all cell lines. Another NHEJ protein KU80 was also repressed to s
