TY - JOUR T1 - Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer JF - Anticancer Research JO - Anticancer Res SP - 161 LP - 168 VL - 36 IS - 1 AU - KAVITHA RAMACHANDRAN AU - CARL SPEER AU - LUBOV NATHANSON AU - MARTHA CLAROS AU - RAKESH SINGAL Y1 - 2016/01/01 UR - http://ar.iiarjournals.org/content/36/1/161.abstract N2 - Background/Aim: Cabazitaxel is an approved second-line treatment for docetaxel-refractory metastatic castration-resistant prostate cancer. However, the median time to progression on cabazitaxel is 2.8 months. We aimed to determine whether DNA methylation plays a role in cabazitaxel resistance. Materials and Methods: DU145 cells, resistant to docetaxel and cabaxitaxel (DU145 10DRCR), were generated from cells resistant to 10 nM docetaxel (DU145 10DR). The effect of pre-treatment with 5-azacytidine was determined with regards to cabazitaxel sensitivity. Gene expression profiling was carried-out on DU145 10DR, DU145 10DRCR and DU145 10DRCR treated with 5-azacytidine. Results: Pre-treatment of cells with 5-azacytidine resulted in enhanced sensitivity to cabazitaxel. Gene expression profiling identified a subset of genes that may be regulated by DNA methylation. Conclusion: Our results indicate that DNA methylation of pro-apoptotic and cell-cycle regulatory genes may contribute to cabazitaxel resistance and pre-treatment with 5-azacytidine may restore sensitivity to cabazitaxel in prostate cancer cells. ER -