Therapeutic targeting of EGFR in malignant gliomas

Despite the improved prognosis for many cancer patients, the survival of those with malignant gliomas (MGs) remains dismal. Even with aggressive intervention, including surgery, chemotherapy and radiotherapy, the overall 2-year survival rate is only 25% in the most optimistic series, and 5-year survival rates are consistently in the low single digits. Therefore, it is evident that novel therapeutic paradigms are necessary to overcome the inherent limitations of conventional treatments. EGFR gene overexpression can be found in 40 - 50% of patients with MGs, whereas its expression is very low in normal brain. Therapeutic targeting of EGFR has indicated clinical success in the treatment of MGs.

The purpose of this review is to discuss the current status of several EGFR-targeted therapies in MGs patients and address the efficacy of these drugs as monotherapy or in combination with other drugs and/or treatments. We also emphasize the lessons learned and the future perspectives in the development of EGFR-targeted therapies for MGs.

A more comprehensive understanding of the molecular, structural and biological characteristics of EGFR and the mechanisms of action of EGFR-targeted antagonists will most likely contribute to the successful use of strategies of EGFR-targeted therapy in the clinic.

Therapeutic targeting of EGFR include anti-EGFR mAbs, small-molecule EGFR tyrosine kinase inhibitors, peptide vaccination therapy and other therapeutic strategies. Each EGFR antagonist has its own advantages and limitations in terms of BBB crossing, ease of delivery, combination therapies and potential toxicity. Therefore, a multiple approach combining different agents that target EGFR signaling at multiple levels seems to have potential as future therapeutics for MGs, once the technical and safety issues unique to each of the approaches are overcome.