Evaluating treatment response in glioblastoma

Glioblastoma is the most prevalent adult primary brain cancer. It is a very aggressive cancer with a dismal outcome. Survival is only ~15 months after diagnosis, despite standard-of-care (SoC) therapy consisting of maximal safe resection, radiotherapy (RT) and chemotherapy (temozolomide). SoC has not changed over the last 20 years and numerous clinical trials evaluating novel therapies have failed. Therapeutic failure can be ascribed to certain inherent properties of glioblastoma, including very high inter- and intra-tumoral heterogeneity, cellular plasticity, communication with stromal cells, among others. Cellular plasticity in glioblastoma can also be driven by treatment itself and forms the basis of treatment resistance. Moreover, many of the currently used models for preclinical research fail to mimic some of these important hallmarks, limiting translation of preclinical findings to patient outcome.

The glioblastoma research at the Radiobiology Unit aims to address some of these issues:
- what are mechanisms of treatment-induced plasticity and treatment resistance?
- can cells be "locked" in a more sensitive state?
- can we develop more suitable preclinical in vitro models for drug/RT testing?
- is targeted radionuclide therapy a viable treatment option for glioblastoma?

The objectives of the bachelor project will consist of:
- optimizing new protocols (e.g. immunostainings, cell death assays) and if successful testing these on treated versus untreated samples of (i) glioblastoma cell lines, (ii) patient-derived glioma stem-like cells, or (iii) glioblastoma assembloid models. 
- assessing treatment-sensitivity of forskolin- and TSA-induced differentiated GBM cells (differentiation therapy).
- characterizing treatment-resistant cell lines utilizing molecular assays (e.g. qPCR, western blotting, immunostaining)