Details

Autor(en) / Beteiligte

• Pawlowski, Kristen D.
• Duffy, Joseph T.
• Babak, Maria V.
• Balyasnikova, Irina V.

Titel

Modeling glioblastoma complexity with organoids for personalized treatments

Ist Teil von

• Trends in molecular medicine, 2023-04, Vol.29 (4), p.282-296

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Glioblastoma (GBM) organoids (GBOs) can be generated through genetic manipulation or by implanting patient-derived tumors into healthy brain organoids.GBOs retain the intra- and interheterogeneity of GBM and recapitulate its aggressiveness and resistance to therapeutics, which has been a limitation of previous GBM models.GBOs spontaneously generate complex extracellular matrices that influence tumor invasion.GBOs helped to identify the ADAM10 inhibitor, GI254023X, to reduce tumor spread.Advances in introducing vasculature, blood–brain barrier, and immune cells within GBOs will assist in identifying anti-angiogenesis agents and studies involving pharmacokinetics and immunotherapy.GBOs are generated from patients promptly, can aid in clinical decision-making, and have a greater predictive value in therapeutic response compared with traditional GBM models. Glioblastoma (GBM) remains a fatal diagnosis despite the current standard of care of maximal surgical resection, radiation, and temozolomide (TMZ) therapy. One aspect that impedes drug development is the lack of an appropriate model representative of the complexity of patient tumors. Brain organoids derived from cell culture techniques provide a robust, easily manipulatable, and high-throughput model for GBM. In this review, we highlight recent progress in developing GBM organoids (GBOs) with a focus on generating the GBM microenvironment (i.e., stem cells, vasculature, and immune cells) recapitulating human disease. Finally, we also discuss the use of organoids as a screening tool in drug development for GBM.