Generation of glioblastoma patient-derived organoids and mouse brain orthotopic xenografts for drug screening

STAR Protoc. 2021 Feb 18;2(1):100345. doi: 10.1016/j.xpro.2021.100345. eCollection 2021 Mar 19.

Abstract

Robust patient-derived platforms that recapitulate the cellular and molecular fingerprints of glioblastoma are crucial for developing effective therapies. Here, we describe a chemically defined protocol for 3D culture and propagation of glioblastoma in 3D gliospheres, patient-derived organoids (PDOs), mouse brain orthotopic xenografts (PDOXs), and downstream drug and immunofluorescence assays. This simple-to-follow protocol allows assessing drug sensitivity, on-target activity, and combined drug synergy. Promising therapies can then be validated in PDOXs for translation in precision medicine oncology trials. For complete details on the use and execution of this protocol, please refer to Chadwick et al. (2020) and Patrizii et al. (2018).

Keywords: Organoids; PDX; combination therapy; drug synergy; glioblastoma; o; orthotopic patient derived xenografts; patient derived organoids; precision medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Brain* / metabolism
  • Brain* / pathology
  • Glioblastoma* / drug therapy
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Organoids* / metabolism
  • Organoids* / pathology
  • Organoids* / transplantation
  • Xenograft Model Antitumor Assays