HDACs remove the acetyl groups from lysine in the histone tail, which promotes more condensed chromatin structure, resulting in the repression of gene transcription by limiting the accessibility of the transcription factors. Increased expression and activity ofHDACsin cancer tissues led to the rational design of histone deacetylase inhibitors as potential therapeutic agents for cancer therapy. Several HDACIs have been used in phase I and II clinical trial for the treatment of a number of hematological malignancies and also solid tumors. Most of the positive responses to HDACIs were found to be in patients with hematological malignancies including cutaneous Tcell lymphoma and peripheral T-cell lymphoma. However, the results in solid tumors, thus far, have been disappointing. To date, several mechanisms by which resistance are induced during the treatment of solid tumors with HDACIs have been elucidated, including increased expression of the multidrug-resistance gene, MDR1, increased anti-apoptotic proteins and activating cell survival pathway, and such findings have not yet been translated into clinical medicine. Therefore, better understanding of the molecular determinants of resistance to HDACIs could provide the basis for the GANT61 development of novel therapeutic strategies that could improve the treatment outcome of patients diagnosed with solid tumors. Epithelial-to-Mesenchymal Transition is believed to be BAY-60-7550 associated with drug-resistance. The biology of EMT is a crucial trans-differentiation process, which occurs during embryogenesis and in adult tissues following wound repair and organ remodeling in response to injury, and also occurs during cancer progression. During this process, the epithelial cells acquire mesenchymal cell morphology through down-regulation of epithelial markers and up-regulation of mesenchymal markers, thereby leads to increased migratory capacity, invasiveness and increased resistance to chemotherapy, and all of which are involved in cancer progression. Moreover, the cells with EMT phenotype share characteristics with cancer stem-like cell, which confers drug resistance to these cells and contributes to cancer recurrence and metastasis. Kong et al., found that over-expression of PDGF-D led to the induction of EMT phenotype in PC3 prostate cancer cells, which was associated with loss of epithelial markers and gain of expression of mesenchymal markers such as N-cadherin, vimentin as well as up-regulation of transcription factors including ZEB1, ZEB2 and Slug, resulting in enhanced cell migration, invasion in vitro and tumor growth in vivo. Furthermore, PDGF-D over-expressing PC3 cells with EMT phenotype displayed CSLC signatures, which was consistent with increased expression of Oct4. Nanog, Sox2 and Lin28B, resulting in enhanced clonogenic ability and self-renewal capacity.