Histone acetylation, controlled by histone acetylases and histone deacetylases, modifies nucleosome and chromatin Torin 1 structures and regulates gene expression. HDACs are overexpressed in colon, breast, prostate and other cancers, making HDACs an attractive anticancer target. HDACs have been divided into four classes: class I, class IIa, class IIb, class III and class IV. Previous studies have demonstrated that HDAC inhibitors reverse the aberrant epigenetic changes associated with various cancers and thus are currently being investigated as possible therapeutics. HDAC inhibitors have been shown to induce tumor cell differentiation, apoptosis, and/or growth arrest in several in vitro and in vivo experimental models. One of these HDAC inhibitors, suberoylanilide hydroxamic acid, has been Food and Drug Administration approved for patients with cutaneous T-cell lymphoma who have failed prior therapies. Data from clinical trials show that SAHA is well tolerated and has limited toxicity which is rapidly reversible upon discontinuation of the drug. SAHA has been shown to inhibit HDAC activity and enhance radiosensitivity in multiple cell lines. However, there is limited data investigating SAHA in the metastatic setting. Recently, it was reported that SAHA inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks. Previous studies have demonstrated that the expression of matrix metalloproteinase-9 has been associated with a high potential of metastasis in several human carcinomas including breast cancer. Our group has shown that HTPB, a novel HDAC inhibitor, inhibits lung cancer cell migration via reduced activities of MMPs, RhoA, and focal adhesion complex. HDAC inhibitors can induce cell-cycle arrest, promote differentiation, stimulate ROS generation, inhibit tumor angiogenesis and induce apoptosis. More recently, HDAC inhibition has been shown to induce autophagy. Autophagy is a catabolic process by which cytosolic material is targeted for lysosomal degradation by means of double-membrane-bound cytosolic vesicles, termed autophagosomes. During autophagy, free cytosolic LC3 becomes conjugated to phosphatidylethanolamide. LC3-II is then incorporated into the growing autophagosome structure that, upon maturation, fuses with the lysosome compartment, leading to the degradation of the autophagosome contents. Autophagic cell death is another important physiological cell death process. SAHA has been reported to induce autophagy, which may contribute to its anticancer activity. The excessive number of cells undergoing ����self-eating���� through autophagy during chemotherapy may trigger cell death by an as yet unknown mechanism. Increasing evidence in the literature shows that DNA damage induces autophagy, but the role of autophagy in the DNA damage response is still unclear. Ionizing radiation leads to cell death through the Rapamycin purchase induction of DSBs. Cells have developed mechanisms to repair such DSBs through two major pathways: non-homologous end joining and homologous recombination. HDACs influence the DNA damage response through the acetylation of key DNA repair and checkpoint proteins. It has been demonstrated that HDAC inhibitors inhibit DNA repair by downregulation or inhibition of the activity of DNA repair proteins, including the components of the NHEJ and HR pathways in cancer cells. Therefore, HDAC inhibitors showed promise as radiosensitizers when administered in combination with radiotherapy. In addition, recent evidence has shown that one of the mechanisms whereby IR activates endoplasmic reticulum stress is by the induction of DNA damage.