title: Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?
abstract: Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered.
authors.affiliation: aResearch Center Jülich (FZJ), Institute of Complex Systems, Jülich bDepartment of Neurosurgery cDepartment of Neuropathology dDepartment of Medical Statistics, RWTH Aachen University, Aachen, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Linz
authors.forename: Baran
authors.initials: B
authors.lastname: Ulus
authors.forename: Georg
authors.initials: G
authors.lastname: Neuloh
authors.forename: Hans
authors.initials: H
authors.lastname: Clusmann
authors.forename: Markus
authors.initials: M
authors.lastname: Oertel
authors.forename: Kay
authors.initials: K
authors.lastname: Nolte
authors.forename: Joachim
authors.initials: J
authors.lastname: Weis
authors.forename: Nicole
authors.initials: N
authors.lastname: Heussen
authors.forename: Joachim M
authors.initials: JM
authors.lastname: Gilsbach
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D016032:Randomized Controlled Trials as Topic; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents