Project Title

Validating diagnostic OMICS tools for target identification and recurrence monitoring in glioblastoma

Acronym

PerCareGlio

General overview of the project

Glioblastoma (GB, former GBM) is the most common aggressive brain tumor. Despite multimodal therapy including surgical resection and radio- and chemotherapy, prognosis for patients is poor (median survival times of < 15 months) and recurrence is common, clearly indicating the unmet medical need for novel personalized treatment options and associated biomarkers for therapy monitoring and optimization. In our previous ERANET project PerProGlio, we identified therapeutically relevant proteomic subtypes from >100 GB patients based on tumor tissues and established GB-associated proteins in serum indicative for GB recurrence. The novel project PerCareGlio builds on these findings. In a multicentric setting, we will determine patient-specific GB (phospho-)proteomes of tumors to be integrated with data analysis aimed at the identification of suitable drug targets for which approved drugs are available. A patient-specific ex vivo platform with cultivation of primary tumor cells derived from individual patients will be developed and drug sensitivity testing will be performed to ascertain clinical relevance and applicability. By linking drug responsiveness to proteomic signatures, PerCareGlio also provides unique reference data for further therapy development. Furthermore, we will perform longitudinal (monthly) serum proteome profiling of GB patients to validate our most prominent recurrence marker proteins (e.g. ASAH1, PAR2, Lumican). Additional miRNA profiling broadens the scope of liquid biopsy monitoring. As overall aims of PerCareGlio, we propose to provide a platform for improved GB patient management covering tumor monitoring, tumor profiling and consecutive therapy decisions to optimize radiochemotherapy, and ultimately to enhance life quality and expectation utilizing a personalized therapy regimen in GB patients.

Main objectives of the project

The project has three major objectives (O1-3), organized in 6 executive work packages + 1 work package for coordination:

O1: Identification of therapeutic vulnerabilities and actionable signaling pathways from individual GB patients by proteome involving data analysis (involving WP1, 2 and 6)

O2: Longitudinal analysis of GB patients (WP1) for recurrence and therapy recommendation based on serum proteomics (WP2b) and serum miRNA profiles (WP3) involving data analysis (WP6)

O3: Ex vivo testing of personalized therapy concepts using a patient-derived GB cell/organoid platform (WP4) and drug sensitivity testing (WP5)

Project duration: 01.05.2025 - 31.12.2027

Consortium: