Targeting the Epidermal Growth Factor Receptor Pathway in Glioblastoma Multiforme and Other Intracranial Malignancies pp.89-106
Authors: (Marc-Eric Halatsch, Georg Karpel-Massler - Dept of Neurosurgery, Univ. of Heidelberg, Heidelberg, Germany)
Abstract: Limited therapeutic options exist for glioblastoma multiforme (GBM), the most common primary central nervous system tumor, and recurrence is common. Standard therapy is surgical resection, where possible, and radiotherapy. Adjuvant chemotherapy provides only a modest survival benefit, and new therapies are urgently needed. Dysregulated epidermal growth factor receptor (HER1/EGFR) is found in 40-50% of GBM. As the intracellular tyrosine kinase (TK) of the HER1/EGFR activates signalling cascades leading to cell proliferation, angiogenesis and inhibition of apoptosis, HER1/EGFR represents an attractive therapeutic target. HER1/EGFR TK inhibitors are in advanced clinical development for glioma, and a number of trials are in progress, or have recently been completed. Although data from experimental studies seem promising, proof of a significant clinical benefit is lacking. A problem that has to be further addressed is the prediction of the individual tumor response to HER1/EGFR TK inhibitors based on molecular determinants. This chapter reviews the role of HER1/EGFR TK inhibitors in the treatment of GBM and other intracranial malignancies.