title: Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sylvester Cancer Center, University of Miami, Miami, FL, U.S.A.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Ramachandran
authors.affiliation: Nova Southeastern University, Miami, FL, U.S.A.
authors.forename: Carl
authors.initials: C
authors.lastname: Speer
authors.affiliation: Nova Southeastern University, Miami, FL, U.S.A.
authors.forename: Lubov
authors.initials: L
authors.lastname: Nathanson
authors.affiliation: Sylvester Cancer Center, University of Miami, Miami, FL, U.S.A.
authors.forename: Martha
authors.initials: M
authors.lastname: Claros
authors.affiliation: Sylvester Cancer Center, University of Miami, Miami, FL, U.S.A. rsingal@med.miami.edu.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Singal
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D043823:Taxoids / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D043823:Taxoids; D000077143:Docetaxel; C552428:cabazitaxel; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: DNA methylation; Epigenetics; drug resistance; prostate cancer