Patient-specific orthotopic glioblastoma xenograft models recapitulate the histopathology and biology of human glioblastomas in situ

Cell Rep. 2013 Jan 31;3(1):260-73. doi: 10.1016/j.celrep.2012.12.013. Epub 2013 Jan 17.


Frequent discrepancies between preclinical and clinical results of anticancer agents demand a reliable translational platform that can precisely recapitulate the biology of human cancers. Another critical unmet need is the ability to predict therapeutic responses for individual patients. Toward this goal, we have established a library of orthotopic glioblastoma (GBM) xenograft models using surgical samples of GBM patients. These patient-specific GBM xenograft tumors recapitulate histopathological properties and maintain genomic characteristics of parental GBMs in situ. Furthermore, in vivo irradiation, chemotherapy, and targeted therapy of these xenograft tumors mimic the treatment response of parental GBMs. We also found that establishment of orthotopic xenograft models portends poor prognosis of GBM patients and identified the gene signatures and pathways signatures associated with the clinical aggressiveness of GBMs. Together, the patient-specific orthotopic GBM xenograft library represent the preclinically and clinically valuable "patient tumor's phenocopy" that represents molecular and functional heterogeneity of GBMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology*
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / surgery
  • Cell Shape
  • Cell Transformation, Neoplastic / pathology
  • Female
  • Genome, Human / genetics
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology*
  • Glioblastoma / radiotherapy
  • Glioblastoma / surgery
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Spheroids, Cellular / pathology
  • Treatment Outcome
  • Xenograft Model Antitumor Assays*
  • Young Adult

Associated data

  • GEO/GSE42670