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

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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.
Funding Information
  • The Sid Faithfull Group
  • the Neurosurgical Research Foundation
  • Tour de Cure
  • the Medical Research Future Fund (MRFF) Rapid Applied Research Translation Program, Centre for Personalised Analysis of Cancers (GA59729, GA59729)
  • NHMRC (2021/GNT2013180 and 2023/GNT2030541)
  • McCleary Murchland Fellowship
  • the Charlie Teo Foundation
  • The MAWA Trust
  • the Medical Research Future Fund (MRFF) Australian Brain Cancer Infrastructure Grant (2023943)

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