Glioblastoma is among the most lethal human cancers and remains incurable despite aggressive multimodal therapy. A major challenge is the inevitable recurrence of tumors after an initial response to the standard chemotherapeutic agent temozolomide (TMZ), frequently accompanied by acquired drug resistance. 

Glioblastoma cells are known to form dense, multicellular tumor networks via ultra-long membrane protrusions, so called tumor microtubes (TMs), enabling intercellular communication that has been shown to contribute to therapy resistance and brain invasion. In preliminary experiments, we observed that glioblastoma cells with acquired TMZ resistance display a structurally reinforced tumor network, characterized by increased TM length and greater number of TM-mediated cell-cell connections. 

Building on this observation, my project explores whether targeted disruption of glioblastoma’s reinforced network architecture can overcome acquired TMZ resistance. We focus on already FDA-approved drugs identified and filtered in cooperations with the MPI in Dortmund, based on their ability to reduce TM length in primary human glioblastoma cells. We now investigate the mechanism underlying these morphological effects and assess whether combining these agents with TMZ yields synergistic activity in TMZ-resistant glioblastoma. 

By elucidation a novel therapeutic vulnerability, this research seeks to refine current models of treatment failure and open a translational path toward network-targeted therapeutic strategies in TMZ-resistant glioblastoma.