Enhancing the Anticancer Activity of Erlotinib in Glioblastoma
Pp. 407-436 (30)
Georg Karpel-Massler, Christian R. Wirtz and Marc-Eric Halatsch
Glioblastoma multiforme (GBM) is the most common malignant intrinsic
brain tumor in adults. Especially in this disease, qualitative and quantitative aspects
render the dysregulated epidermal growth factor receptor (HER1/EGFR) an outstanding
therapeutic target. A variety of therapeutic compounds was developed to target
HER1/EGFR among which the clinically most advanced agents are small molecule
tyrosine kinase (TK) inhibitors. Unfortunately, clinical studies examining their
therapeutic efficacy have so far failed to document a major therapeutic break-through in
the setting of GBM. Thus, the targeted approach against HER1/EGFR likely requires a
synergistic drug combination strategy to ultimately become successful in this disease.
This patents chapter focuses on innovative therapeutic strategies combining
HER1/EGFR-targeted TK inhibitors with novel agents which for the most part have not
been evaluated for the treatment of GBM yet but which constitute interesting candidates
for further evaluation in this setting.
Angiogenesis, combination therapy, erlotinib, glioblastoma,
HER1/EGFR, high-grade glioma, histone deacetylase inhibitors, IGF1R, Kit,
multi-targeting, neurooncology, oncogene, pralatrexate, radiotherapy, romidepsin,
targeted therapy, temozolomide, tumorigenesis, tyrosine kinase inhibitor, vascular
Department of Neurosurgery, University of Ulm School of Medicine, Albert-Einstein-Allee 23, D-89081 Ulm, Germany.