Biobanked Glioblastoma Patient-Derived Organoids as a Precision Medicine Model to Study Inhibition of Invasion

Int J Mol Sci. 2021 Oct 3;22(19):10720. doi: 10.3390/ijms221910720.


Glioblastoma (GBM) is highly resistant to treatment and invasion into the surrounding brain is a cancer hallmark that leads to recurrence despite surgical resection. With the emergence of precision medicine, patient-derived 3D systems are considered potentially robust GBM preclinical models. In this study, we screened a library of 22 anti-invasive compounds (i.e., NF-kB, GSK-3-B, COX-2, and tubulin inhibitors) using glioblastoma U-251 MG cell spheroids. We evaluated toxicity and invasion inhibition using a 3D Matrigel invasion assay. We next selected three compounds that inhibited invasion and screened them in patient-derived glioblastoma organoids (GBOs). We developed a platform using available macros for FIJI/ImageJ to quantify invasion from the outer margin of organoids. Our data demonstrated that a high-throughput invasion screening can be done using both an established cell line and patient-derived 3D model systems. Tubulin inhibitor compounds had the best efficacy with U-251 MG cells, however, in ex vivo patient organoids the results were highly variable. Our results indicate that the efficacy of compounds is highly related to patient intra and inter-tumor heterogeneity. These results indicate that such models can be used to evaluate personal oncology therapeutic strategies.

Keywords: compound; drug screening; glioblastoma; invasion; organoids; patient-derived; precision medicine.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biological Specimen Banks*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Drug Discovery* / methods
  • Drug Screening Assays, Antitumor / methods
  • Glioblastoma / drug therapy
  • Glioblastoma / pathology*
  • Humans
  • Neoplasm Invasiveness
  • Organoids*
  • Precision Medicine* / methods
  • Spheroids, Cellular
  • Tissue Culture Techniques


  • Antineoplastic Agents