title: Cabazitaxel overcomes cisplatin resistance in germ cell tumour cells.
abstract: BACKGROUND
  Cisplatin-based chemotherapy is highly effective in metastasized germ cell tumours (GCT). However, 10-30 % of patients develop resistance to cisplatin, requiring salvage therapy. We investigated the in vitro activity of paclitaxel and the novel taxane cabazitaxel in cisplatin-sensitive and -resistant GCT cell lines.
  
  
  METHODS
  In vitro activity of paclitaxel and cabazitaxel was determined by proliferation assays, and mode of action of cabazitaxel was assessed by western blotting and two screening approaches, i.e. whole proteome analysis and a human apoptosis array.
  
  
  RESULTS
  Activity of paclitaxel and cabazitaxel was not affected by cisplatin resistance, suggesting that there is no cross-resistance between these agents in vitro. Cabazitaxel treatment showed a strong inhibitory effect on colony formation capacity. Cabazitaxel induced classical apoptosis in all cell lines, reflected by cleavage of PARP and caspase 3, without inducing specific changes in the cell cycle distribution. Using the proteomic and human apoptosis array screening approaches, differential regulation of several proteins, including members of the bcl-2 family, was found, giving first insights into the mode of action of cabazitaxel in GCT.
  
  
  CONCLUSIONS
  Cabazitaxel shows promising in vitro activity in GCT cells, independent of levels of cisplatin resistance.
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Gerwing
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Jacobsen
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.|Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch, Russian Academy of Sciences, Prospect 100 Let Vladivostoku 159, Vladivostok, Russia, 690022.|School of Natural Sciences, Far East Federal University, Sukhanova Street 8, Vladivostok, Russia, 690950.
authors.forename: Sergey
authors.initials: S
authors.lastname: Dyshlovoy
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hauschild
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Rohlfing
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Oing
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, University of Greifswald, Fleischmannstraße 42-44, 17475, Greifswald, Germany.|Department of Functional Genomics, Interfacultary Institute of Genetics and Functional Genomics, University of Greifswald, Friedrich-Ludwig-Jahn-Straße 15 a, 17487, Greifswald, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Venz
authors.affiliation: Department of Oncology, Akershus, University Hospital, POB 1000, 1478, Lørenskog, Norway.|University of Oslo, Blindern, P.O. Box 1072, 0316, Oslo, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Oechsle
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany.
authors.forename: Gunhild
authors.initials: G
authors.lastname: von Amsberg
authors.affiliation: Department of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Martinistaße 52, 20246, Hamburg, Germany. friedemann.honecker@zetup.ch.|Tumor and Breast Center ZeTuP, Rorschacher Strasse 150, 9006, St. Gallen, Switzerland. friedemann.honecker@zetup.ch.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Honecker
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology*; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; C552428:cabazitaxel; D017239:Paclitaxel; D002945:Cisplatin
keywords: Apoptosis; Cabazitaxel; Cisplatin resistance; Germ cell tumour