Personalising glioblastoma medicine: explant organoid applications, challenges and future perspectives.

in Acta neuropathologica communications by Niclas Skarne, Rochelle C J D'Souza, Helen M Palethorpe, Kylah A Bradbrook, Guillermo A Gomez, Bryan W Day

TLDR

  • The study reviews the current state of brain cancer organoid technologies with a focus on GBOs, highlighting their potential to enhance next-generation omics efforts and guide personalized medicine approaches.
  • GBOs are a 3D in vitro culture system that retain brain cancer heterogeneity and transiently maintain the TME, holding significant promise as a translational tool.
  • The study calls for continued research and development of GBOs to overcome their current limitations and optimize their potential for advancing preclinical research and personalized medicine approaches.

Abstract

Glioblastoma (GBM) is a highly aggressive adult brain cancer, characterised by poor prognosis and a dismal five-year survival rate. Despite significant knowledge gains in tumour biology, meaningful advances in patient survival remain elusive. The field of neuro-oncology faces many disease obstacles, one being the paucity of faithful models to advance preclinical research and guide personalised medicine approaches. Recent technological developments have permitted the maintenance, expansion and cryopreservation of GBM explant organoid (GBO) tissue. GBOs represent a translational leap forward and are currently the state-of-the-art in 3D in vitro culture system, retaining brain cancer heterogeneity, and transiently maintaining the immune infiltrate and tumour microenvironment (TME). Here, we provide a review of existing brain cancer organoid technologies, in vivo xenograft approaches, evaluate in-detail the key advantages and limitations of this rapidly emerging technology, and consider solutions to overcome these difficulties. GBOs currently hold significant promise, with the potential to emerge as the key translational tool to synergise and enhance next-generation omics efforts and guide personalised medicine approaches for brain cancer patients into the future.

Overview

  • This study reviews the current state of brain cancer organoid technologies with a focus on glioblastoma explant organoids (GBOs)
  • The study aims to evaluate the advantages and limitations of this emerging technology and explore potential solutions to overcome its difficulties
  • The authors discuss the potential for GBOs to enhance next-generation omics efforts and guide personalized medicine approaches for brain cancer patients

Comparative Analysis & Findings

  • GBOs are a 3D in vitro culture system that retain brain cancer heterogeneity and transiently maintain the immune infiltrate and tumour microenvironment (TME)
  • Compared to other brain cancer organoid technologies, GBOs hold significant promise as a translational tool for advancing preclinical research and personalized medicine approaches
  • In vivo xenograft approaches are limited by their lack of tumour heterogeneity and limited representation of the TME

Implications and Future Directions

  • GBOs have the potential to emerge as a key translational tool for synergizing and enhancing next-generation omics efforts and guiding personalized medicine approaches for brain cancer patients
  • The study highlights the need for continued research and development of GBOs to overcome their current limitations
  • Future studies should focus on optimizing GBO culture conditions, improving tumour heterogeneity, and better mimicking the TME