Project information
Proteomic Portrait of Glioblastoma: a way to Stratified Therapy (PROGLI)

Glioblastoma (GBM) is the most aggressive and common primary brain tumor in adults. Standard treatments include surgery, chemotherapy, and radiotherapy, but the prognosis remains poor, with an overall survival rate of about 21.8 months.
Advancements in GBM treatment depend on identifying aberrantly regulated biological processes. Research is also focused on uncovering new membrane proteins in tumor cells, which can be used as markers for targeting by antibody-drug conjugates or immunotherapy. While genomic and transcriptomic methods have identified some GBM alterations and immune markers, proteomic analyses have lagged due to limited sensitivity and accuracy.
Recent breakthroughs in high-throughput mass spectrometry, capable of quantifying thousands of proteins, open new avenues for in-depth studies of GBM subtype classification, biomarker identification, and elucidation of molecular mechanisms.
This project aims to utilize advanced proteomic techniques to identify primary GBM (pGBM) patient subgroups with distinct proteomic landscapes. Differences in biological processes and their regulators between normal brain tissue and pGBM samples will be characterized. The functional impact of key signaling inhibitors will be evaluated using 3D tumor models derived from patient tissue and spheroids established from cell lines. To mitigate resistance development, we will identify combinations of core protein inhibitors addressing pGBM heterogeneity, tumor plasticity, and adaptations.
To enhance the clinical translation of our project, we will prioritize the testing of drugs in late-stage clinical trials or already approved medicaments. If non-druggable biotargets are identified, the functional impact of their manipulation will be determined using molecular biology techniques such as CRISPR Cas9 and siRNA.