GBM is the most common and aggressive malignant brain cancer, with a 5-year survival rate of less than 7%. Despite surgery and radiochemotherapy, recurrence is nearly inevitable and almost always fatal. However, the mechanisms driving treatment resistance and recurrence remain poorly understood. This project aims to profile primary and recurrent GBM pairs, along with matched patient-derived organoid models, using single-cell and bulk sequencing approaches. The goal is to identify cellular populations and regulatory programs enriched or activated in treated samples, providing insights into the underlying mechanisms of treatment resistance and potentially leading to improved outcomes for GBM patients. We also aim to compare matched tissues and organoid models to assess how well these models recapitulate the transcriptional and regulatory features of tumors.