Glioblastoma, an aggressive brain tumor, frequently involves aberrant activation of the growth signaling EGF receptor (EGFR). However, inhibitors of EGFR – which are therapeutically effective against other types of EGFR-driven cancer – have limited clinical benefits against glioblastoma.
Jialiang Wang, Ph.D., and colleagues examined whether activation of another growth signaling pathway confers resistance to EGFR inhibitors in glioblastoma. They showed, using patient-derived glioblastoma cell lines, that activation of the insulin receptor (InsR) and insulin-like growth factor 1 receptor (IGF1R) protected a majority of cell lines from the EGFR inhibitor gefitinib. A combination of gefitinib and a dual InsR/IGF1R inhibitor was more effective than either agent alone against glioblastoma xenograft tumors in a mouse model.
The findings, reported in the April 1 issue of Clinical Cancer Research, suggest that activation of the InsR/IGF1R pathway confers resistance to EGFR inhibitors in glioblastoma. Combining therapies that block both pathways may be a promising treatment for EGFR-dependent glioblastoma.
This research was supported in part by the Southeastern Brain Tumor Foundation, the Voice Against Brain Cancer Foundation, and a grant from the National Cancer Institute (CA166492).
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