Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma.

ABSTRACT:

Purpose

Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying novel therapeutic opportunities.

Experimental design

We developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs.

Results

These studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurr

SUBMITTER: Al-Holou WN 

PROVIDER: S-EPMC9841165 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature