title: A novel 3D human glioblastoma cell culture system for modeling drug and radiation responses.
abstract: Glioblastoma (GBM) is the most common primary brain tumor, with dismal prognosis. The failure of drug-radiation combinations with promising preclinical data to translate into effective clinical treatments may relate to the use of simplified 2-dimensional in vitro GBM cultures.
  
  
  
  We developed a customized 3D GBM culture system based on a polystyrene scaffold (Alvetex) that recapitulates key histological features of GBM and compared it with conventional 2D cultures with respect to their response to radiation and to molecular targeted agents for which clinical data are available.
  
  
  
  In 3 patient-derived GBM lines, no difference in radiation sensitivity was observed between 2D and 3D cultures, as measured by clonogenic survival. Three different molecular targeted agents, for which robust clinical data are available were evaluated in 2D and 3D conditions: (i) temozolomide, which improves overall survival and is standard of care for GBM, exhibited statistically significant effects on clonogenic survival in both patient-derived cell lines when evaluated in the 3D model compared with only one cell line in 2D cells; (ii) bevacizumab, which has been shown to increase progression-free survival when added to standard chemoradiation in phase III clinical trials, exhibited marked radiosensitizing activity in our 3D model but had no effect on 2D cells; and (iii) erlotinib, which had no efficacy in clinical trials, displayed no activity in our 3D GBM model, but radiosensitized 2D cells.
  
  
  
  Our 3D model reliably predicted clinical efficacy, strongly supporting its clinical relevance and potential value in preclinical evaluation of drug-radiation combinations for GBM.
authors: Wolfson Wohl Translational Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors: Natividad
authors: N
authors: Gomez-Roman
authors: Wolfson Wohl Translational Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors: Katrina
authors: K
authors: Stevenson
authors: Wolfson Wohl Translational Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors: Lesley
authors: L
authors: Gilmour
authors: Wolfson Wohl Translational Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors: Graham
authors: G
authors: Hamilton
authors: Wolfson Wohl Translational Cancer Research Center, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
authors: Anthony J
authors: AJ
authors: Chalmers
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D015195:Drug Design; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011878:Radiotherapy; D018874:Spheroids, Cellular / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents
keywords: VEGF; erlotinib; glioblastoma; glioma stemlike cells; ionizing radiation; three-dimensional