Fighting the multidimensional burden of intratumoral plasticity: investigation of single cell transcriptional-morphological relationships as a novel avenue to overcome therapy resistance in glioblastoma

Our research focuses on novel treatment strategies geared towards the isolation of glioblastoma cells within syncytial network architectures. We are establishing long-term cultures of glioblastoma cells and tumor organoids in human neocortical brain slices as a highly-clinically relevant glioblastoma model. Three-dimensional tumor networks are reconstructed based on two-photon imaging data and matched to therapy-induced transcriptional dynamics on the single cell level. Based on our preliminary data we have initiated a nation-wide early clinical trial which will evaluate feasibility of a novel therapeutic approach of a tumor cell isolation within the malignant spatial network. Glioblastoma specimens from treated patients within this clinical trial will serve as a validation tool for our preclinical findings.