MGMT

This study established 18 patient-derived glioblastoma organoid (GBO) lines that faithfully preserve the histopathological and genomic features of parental tumors. Glioblastoma organoid-based drug sensitivity testing (GBO-DST) demonstrated a strong correlation with progression-free survival and proved superior to MGMT methylation status in predicting temozolomide response. Transcriptomic analysis elucidated mechanisms of temozolomide resistance, including mismatch repair deficiency and elevated MGMT expression. Furthermore, FDA-approved drug screening using GBO-DST identified regorafenib and lazertinib as effective therapeutic alternatives, with lazertinib showing superior efficacy in a GBO transplantation mouse model. These findings highlight the significant potential of GBO-DST as a robust platform for precision oncology in glioblastoma.

This single-center retrospective study investigated the prognostic impact of MGMT promoter methylation and TERT promoter mutations in 54 patients with WHO grade 4 glioblastoma. The findings indicate that MGMT methylation is independently associated with improved overall survival, whereas TERT mutations predict worse survival. Adjuvant chemoradiotherapy was also confirmed to improve outcomes. A combined stratification using both biomarkers allows for the identification of four distinct prognostic subgroups, with MGMT-methylated/TERT-wild-type patients exhibiting the longest survival.