Glioblastoma multiforme (GBM) remains a highly aggressive brain tumor with limited
treatment options and a poor prognosis. Temozolomide (TMZ) is the only approved
first-line therapy, but frequent resistance limits its efficacy, highlighting the urgent
need for alternative treatments. Patient-derived glioblastoma organoids (GBOs) offer a
promising preclinical model for personalized drug testing and therapy development.
In our previous study, we established 20 GBO lines using a serum-free protocol,
preserving the histopathological and genomic features of the parental tumors.
Additionally, GBO Drug Sensitivity Testing (GBO-DST) was developed to evaluate TMZ
responsiveness and to screen several FDA-approved drugs, including Lazertinib and
Regorafenib. The GBO-DST was successfully validated by correlating IC50 values with
progression-free survival, GBO size measurement after treatment, and histopathological
evaluation.
The goal of this study is to investigate whether a preclinical model using GBOs can
eventually replace clinical trials. Therefore, it is necessary to collect diverse genetic
information from patients in a multicenter setting, along with corresponding GBOs that
recapitulate the patient tumors. Using GBO-DST, external cohort validation will be
performed. Concurrently, the study aims to predict the potency of multi-kinase inhibitors
or EGFR-TKIs, which are expected to show efficacy based on prior research, and compare
these predictions against clinical outcomes.
This study aims to establish 100 GBO lines, targeting the enrollment of 150 patients,
considering a previous success rate of 66.7% for GBO establishment. Since the study
requires tumor tissue and genetic information from patients, IRB approvals from multiple
institutions have been secured (including five tertiary hospitals in South Korea:
Chungnam National University Hospital, Soonchunhyang University Hospital, Keimyung
University Hospital, Yeungnam University Hospital, and Dong-A University Hospital).
However, as this study retrospectively correlates patient clinical outcomes with GBO-DST
results, it does not involve direct interventions with patients. Specifically, GBO-DST
results for multiple candidate drugs will not be used to alter patients' treatment
regimens.
The study collects clinical information and genetic data from patients, with clinical
outcomes defined as progression-free survival and overall survival. Radiologic data will
be prospectively collected to achieve these objectives.
Through this study, we aim to validate the findings of previous research by confirming
that GBO-DST accurately recapitulates patients' drug responses. Furthermore, we seek to
establish GBO-DST as a preclinical trial platform capable of replacing traditional
clinical trials.
