Glioblastomas: HER1/EGFR-Targeted Therapeutics

Abstract

The most common primary brain tumors are gliomas. Glioblastoma is the most malignant subtype and accounts for more than 50% of all gliomas. Patients with glioblastoma still face a poor prognosis, despite treatment according to the current standards of care. Thus, great effort is made to identify more successful therapeutic strategies. The epidermal growth factor receptor (HER1/EGFR) is one of the targets being in the focus of intense investigation. In 40-50% of glioblastoma dysregulation of HER1/EGFR is found and its overexpression represents one of the most common molecular abnormalities seen in high-grade gliomas. Various compounds have been developed to target HER1/EGFR or its mutant form, EGFRvIII. Clinical data is so far most advanced for tyrosine kinase (TK) inhibitors. But also radio-immuno conjugates, ligand-toxin conjugates, antibodies, RNA-based agents and vaccines have been developed and investigated on to a various extent. Unfortunately, the initial enthusiasm derived by promising results from experimental studies could not be confirmed by clinical studies. It seems that inhibition of solely HER1/EGFR is insufficient to provide a clinical benefit. Therefore, a multi-targeted approach tailored to the individual molecular pattern might be a more successful therapeutic strategy.