Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma.

ABSTRACT:

Background

Glioblastoma (GBM) is the most common primary malignant adult brain tumor. Temozolomide (TMZ) is the standard of care and is most effective in GBMs that lack the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Moreover, even initially responsive tumors develop a secondary resistance to TMZ and become untreatable. Since aberrant epidermal growth factor receptor (EGFR) signaling is widespread in GBM, EGFR inhibition has been tried in multiple clinical trials without success. We recently reported that inhibiting EGFR leads to increased secretion of tumor necrosis factor (TNF) and activation of a survival pathway in GBM. Here, we compare the efficacy of TMZ versus EGFR plus TNF inhibition in an orthotopic mouse model of GBM.

Methods

We use an orthoto

SUBMITTER: Guo G 

PROVIDER: S-EPMC6917414 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature