Glioblastoma resistance to EGFR antibody-drug conjugate is driven by transcriptional reprogramming and TEK-induced EGFR suppression.

ABSTRACT:

Background

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, remains uniformly fatal due to the lack of effective targeted therapies. The epidermal growth factor receptor (EGFR) is the most frequently altered receptor tyrosine kinase oncogene in GBM with most alterations impacting the receptor ectodomain function, including gene amplification, mutation, rearrangement, and splicing site changes, which occur in approximately 50% of GBM tumors. Depatuxizumab mafodotin (Depatux-M; ABT-414), an antibody-drug conjugate composed of an EGFR-specific antibody (ABT-806) that recognizes the EGFR ectodomain linked to the cytotoxic agent monomethyl auristatin F, initially showed clinical promise. However, it failed to improve survival in phase III trials, highlighting

SUBMITTER: Blomquist MR 

PROVIDER: S-EPMC12542039 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature