Implementing a meningioma organoid platform for testing new treatment approaches

Abstract

Meningioma represents the most common type of brain tumor, accounting for approximately 38.3% of all cases. Despite its prevalence, severe symptoms and potential lethality in high-grade forms, current therapeutic strategies remain limited to surgery and radiotherapy. The risk of recurrency is high. Up to date there are no established pharmacological treatments available. <br /> This thesis explores the development of meningioma organoids. Various culturing techniques were evaluated. Suspension-based methods, such as low-attachment plate cultures and the CERO bioreactor were the most effective. Those methods led to the best meningioma organoid growth in size as well as in number. The resulting organoids resembled the fresh tumor samples derived from patients. Additionally, the feasibility of establishing a meningioma organoid biobank was demonstrated by successfully generating organoids from cryopreserved tumor tissue. Drug testing using the AKT-inhibitor capivasertib and the CDK 4/6-inhibitor abemaciclib showed decreased proliferation, determined by reduced <em>Ki-67</em> mRNA expression. Interestingly, capivasertib treatment led to an unexpected increase in phosphorylated GSK protein levels, suggesting complex pathway dynamics. <br /> Overall, this work establishes a platform for meningioma organoid culture and highlights its potential as a tool for drug screening and the future development of targeted pharmacological therapies.