Characterization of EGFR-reprogrammable temozolomide-resistant cells in a model of glioblastoma.

ABSTRACT: Temozolomide (TMZ) resistance is a major clinical challenge for glioblastoma (GBM). O⁶-methylguanine-DNA methyltransferase (MGMT) mediated DNA damage repair is a key mechanism for TMZ resistance. However, MGMT-null GBM patients remain resistant to TMZ, and the process for resistance evolution is largely unknown. Here, we developed an acquired TMZ resistant xenograft model using serial implantation of MGMT-hypermethylated U87 cells, allowing the extraction of stable, TMZ resistant (TMZ-R) tumors and primary cells. The derived tumors and cells exhibited stable multidrug resistance both in vitro and in vivo. Functional experiments, as well as single-cell RNA sequencing (scRNA-seq), indicated that TMZ treatment induced cellular heterogeneity including quiescent cancer stem cells (CS

SUBMITTER: Gong L 

PROVIDER: S-EPMC9622861 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature