Glioblastoma is the most common malignant primary brain tumor in adults, with a median survival of about 15 months. Standard treatment involves maximal surgical resection, followed by radiation therapy and chemotherapy (temozolomide). Despite this multimodal treatment, survival gains are limited, and tumor recurrence is inevitable. No effective second-line treatment exists.

A major challenge in the development of novel glioblastoma treatments, is intratumoral heterogeneity, which is reflected by the coexistence of multiple phenotypically distinct malignant subclones within a single tumor. These subclones are driven by different oncogenic alterations, some of them in receptor tyrosine kinases. Small-molecule inhibitors targeting these oncoproteins, show strong cytostatic effects in cell lines but haven't improved survival in clinical trials. This highlights the gap between preclinical success and patient benefit, emphasizing the need for novel preclinical models to better understand treatment resistance and the development of new treatments.

Patient derived glioblastoma organoids have shown to retain the genetic and phenotypic heterogeneity in culture and are useful, patient-representative models for studying relevant drug resistance/adaptive pathways also seen in patients.