Designing precision therapies for glioblastoma using next- generation, single cell functional diagnostics
Glioblastoma (GBM) is the most aggressive brain cancer in adults. In spite of intensive treatment, median survival is still only 15 months. Reasons that explain failure to develop more efficient therapies include the high invasiveness of the tumor, its complex genetics, and interpatient and intra-tumoral heterogeneity. Understanding and mapping the complexity of the different tumour cell populations and how each of these respond to therapy, remains one of the largest challenges that prevent the development of suitable therapies. In addition, the development of so-called “functional diagnostic assays” in which the sensitivity of tumor cells is directly measured in functional tests, could speed up the implementation of personalized treatments. In this project, I will develop functional diagnostic assays using patient-derived cell lines (PDCLs) by exposing them to various treatments. As PDCLs commonly consist of various tumor cell subpopulations, I will focus on single cell analysis to study how each of the different tumor cell populations respond to each treatment by implementing state-of-the-art technologies. This will allow me to provide better insights in (i) the various drug sensitivities of heterogeneous GBM tumor cell populations, (ii) disease mechanisms, and (iii) identify putative biomarkers – all of which will be useful in the selection of suitable drug combinations, the design of companion diagnostic assays, and providing inclusion criteria for future clinical trials.