InsR/IGF1R Pathway Mediates Resistance to EGFR Inhibitors in Glioblastoma.

ABSTRACT:

Purpose

Aberrant activation of EGFR is a hallmark of glioblastoma. However, EGFR inhibitors exhibit at best modest efficacy in glioblastoma. This is in sharp contrast with the observations in EGFR-mutant lung cancer. We examined whether activation of functionally redundant receptor tyrosine kinases (RTKs) conferred resistance to EGFR inhibitors in glioblastoma.

Experimental design

We collected a panel of patient-derived glioblastoma xenograft (PDX) lines that maintained expression of wild-type or mutant EGFR in serial xenotransplantation and tissue cultures. Using this physiologically relevant platform, we tested the abilities of several RTK ligands to protect glioblastoma cells against an EGFR inhibitor, gefitinib. Based on the screening results, we further developed a comb

SUBMITTER: Ma Y 

PROVIDER: S-EPMC4818693 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature