Mechanisms, prognostic and predictive biomarkers of glioblastoma

Glioblastoma (GBM), the most frequent and aggressive primary brain cancer, has not gained from recent advances in cancer therapies and remains incurable.

The majority of patients die within one year of diagnosis of a tumor relapse in close proximity to the resection border of the primary tumor.

Our proposal is focused on understanding the biology of the treatment-escaping GBM cells with the goal to produce clinically relevant knowledge and models of GBM that will improve patient survival.

In one project we will isolate and investigate the rarely studied GBM edge cells located just outside of the visible tumor border.

From a pilot study we can show that cultures from edge samples display distinct functional and molecular properties compared to bulk tumor cells.

We will now build on this with more patients and several edge samples from each patient to uncover the biology and spectrum of heterogeneity of GBM edge cells.

GBM edge cell models will be used to develop a novel therapy that attracts, collects and neutralizes these locally invasive, relapse-causing cells.

In another project we aim to uncover the underlying mechanisms of two recently identified molecular GBM subgroups that exhibit significantly different patient survival.

Our analyses show that survival cannot be related to any known prognostic markers which provides an excellent opportunity to identify new mechanisms and biomarkers determining response to standard of care oncological therapy.