Glioblastoma (GB, former GBM) is the most common aggressive brain tumour. Despite multimodal therapy, including surgical resection and radio- and chemotherapy, the prognosis for patients is poor (median survival times of < 15 months), and recurrence is common, clearly indicating the unmet medical need for novel personalised treatment options and associated biomarkers for therapy monitoring and optimisation. Using multi-omic approaches, we have previously identified at least four distinct clusters in >100 GB patients from which therapeutic targets can be discerned. The project PerCareGlio builds on these findings, and we will determine close-to-surgery patient-specific GB (phospho-)proteomes of tumours to be integrated with data analysis aimed to identify suitable drug targets in addition to the standard therapy regimen. A concomitant patient-specific ex vivo platform with the cultivation of primary tumour cells derived from individual patients will be developed so that drug sensitivity testing will be performed to ascertain clinical relevance and applicability. By linking drug responsiveness to proteomic signatures, PerCareGlio provides unique reference data for further development of therapy regimens. Furthermore, we will perform longitudinal (monthly) serum proteome profiling of GB patients to validate our most promising recurrence marker proteins (e.g. ASAH1, PAR2, Lumican). Additional longitudinal serum miRNA profiling will broaden the scope of liquid biopsy monitoring. As the overall aims of PerCareGlio, we propose to provide a platform for improved GB patient management covering tumour monitoring, tumour profiling and consecutive therapy decisions to optimise radiochemotherapy and, ultimately, enhance life quality and expectation utilising a personalised therapy regimen in GB patients.