Targeting heterodimeric EGFR/ErbB2-receptor complexes with novel bispecific small-molecule tyrosine kinase inhibitors in combination with an experimental radiotherapy in human malignant glioma cells

Targeted molecular therapies against the EGF-receptor are novel, promising and potentially radio sensitizing therapeutic approaches in the treatment of glioblastoma (GBM), a highly malignant and treatment refractory brain tumor. As specific EGFR-inhibition rendered up to date only disappointing clinical results, the aim of the present study was to evaluate bispecific EGFR/ErbB2-inhibition. GBM-cell lines with different co-expression levels of EGFR and ErbB2-receptor were treated with specific EGFR- and bispecific EGFR/ErbB2 tyrosine kinase inhibitors (TKIs) and experimental radiotherapy. The results underline the importance of the ErbB2-receptor for GBM cells and the potential clinical importance of bispecific EGFR/ErbB2-tyrosine kinase inhibitors, as EGFR/ErbB2-TKIs overcame cellular resistance against specific EGFR-TKIs and showed radio sensitizing properties.