A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma.

ABSTRACT:

Purpose

Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy.

Experimental design

To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy. We further used two independent validation cohorts of paired clinical tissues to test our findings. Follow-up preclinical treatment strategies were evaluated in patient-derived xenografts.

Results

We describe, in clinical samples, an archetype of rare ALDH1A

SUBMITTER: Kebir S 

PROVIDER: S-EPMC9843437 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature