Focus on glioblastoma: using patient-derived cell lines to decipher tumour expansion and evaluate new treatments

Research Project, 2019 – 2021

In this proposal, we will implement a cross-disciplinary research program to target glioblastoma, the most common form of brain cancer. In the affected patient, a glioblastoma expands gradually through brain tissue, disrupting vital functions. Previously, the development of glioblastoma drugs has been curbed by a lack of valid model systems and the complex genetic heterogeneity across cases - factors that make it hard to accurately assess new therapies and predict responses in the individual patient. To address this shortage, we will develop a large panel of patient-derived cancer stem cell (CSC) cultures of 160 well characterised Swedish cases.

Using this resource, we will combine mathematical and experimental approaches to unlock tumour expansion and define the spectrum of therapeutically relevant regulatory differences between patients. This will help elucidate mechanisms of action and enable accurate targeting of disease subgroups. New therapeutic strategies will subsequently be tested in a mouse model.

The proposed project is the first systems-scale study of cancer expansion across multiple well-characterised patient samples. We make a unique contribution by bridging clinical sample collection with deep molecular characterisation of cells and systems modelling, using methods beyond state-of-the-art. Extensive preliminary data, including a 160 CSC biobank, proof of concept screens and modelling, as well as mouse and human ethics approvals, support the project.