title: Sensitivity Profiles of Human Prostate Cancer Cell Lines to an 80 Kinase Inhibitor Panel.
abstract: BACKGROUND
  Taxanes and anti-androgen therapies are routinely used for the treatment of metastatic prostate cancer, however the majority of patients eventually develop resistance.
  
  
  METHODS
  Eighty kinase inhibitors were screened regarding their ability to inhibit cell viability in CWR22, 22Rv1, PC-3 and DU145 prostate cancer cells using automated toxicity assays. Four kinase inhibitors were selected for further investigation.
  
  
  RESULTS
  No significant difference in sensitivity patterns was found between the androgen receptor wild-type CWR22 and its androgen receptor mutant variant 22Rv1, indicating that androgen receptor mutation did not impact on kinase inhibitor sensitivity in this model. Metastatic PC-3 and DU145 prostate cancer cell lines were less sensitive to kinase inhibitors than the non-metastatic CWR22 and 22Rv1. All four cell lines responded to GSK-3 inhibitor BIO, and MEK inhibitor PD198306. DU145 cells were resistant to p75NTR/TrkA and CHK4 inhibitors, RO-082750 and Ryuvidine.
  
  
  CONCLUSIONS
  Kinase inhibition may be an appropriate strategy for the treatment of prostate cancer.
authors: Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland.
authors: Amy J
authors: AJ
authors: Burke
authors: Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland.
authors: Husnain
authors: H
authors: Ali
authors: Screening Core, National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland.
authors: Enda
authors: E
authors: O'Connell
authors: Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland HRB Clinical Research Facilities Galway, National University of Ireland Galway, Galway, Ireland.
authors: Francis J
authors: FJ
authors: Sullivan
authors: Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland Apoptosis Research Centre, National University of Ireland Galway, Galway, Ireland sharon.glynn@nuigalway.ie.
authors: Sharon A
authors: SA
authors: Glynn
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000737:chemistry*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D047428:Protein Kinase Inhibitors; D011944:Receptors, Androgen; D011494:Protein Kinases
keywords: Prostate cancer; androgen receptor; kinase inhibitors; resistance; therapy