Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma

Int J Mol Sci. 2022 Jun 12;23(12):6572. doi: 10.3390/ijms23126572.


An obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors. Here, we describe our establishment of a PD-GBO-based functional profiling platform and the results of its application to four patient tumors. We show that our PD-GBO model system preserves key features of individual patient glioblastomas in vivo. As proof of concept, we tested a panel of 41 FDA-approved drugs and were able to identify potential treatment options for three out of four patients; the turnaround from tumor resection to discovery of treatment option was 13, 14, and 15 days, respectively. These results demonstrate that this approach is a complement and, potentially, an alternative to current molecular profiling efforts in the pursuit of effective personalized treatment discovery in a clinically relevant time period. Furthermore, these results warrant the use of PD-GBO platforms for preclinical identification of new drugs against defined morphological glioblastoma features.

Keywords: drug profiling; glioblastoma; intercellular calcium waves (ICW); patient-derived organoids; personalized oncology; precision medicine; tumor cell network; tumor microtube (TM).

MeSH terms

  • Glioblastoma* / pathology
  • Humans
  • Models, Biological
  • Neoplasm Recurrence, Local / drug therapy
  • Organoids / pathology