Targeting apoptosis pathways in glioblastoma.
The treatment of glioblastoma remains a major challenge for clinicians since these highly aggressive brain tumors are relatively resistant towards radio- and chemotherapy. The pathways that control apoptosis are altered in glioblastoma cells leading to resistance towards apoptotic stimuli in general. In this review we describe the alterations affecting the p53 pathway, the BCL-2 protein family, the inhibitor of apoptosis proteins and several growth factor pathways involved in the regulation of programmed cell death and define possible targets for new therapies within these apoptotic pathways in glioblastomas. Moreover, we review strategies to target death receptor pathways, most notably to render the glioblastoma cells more susceptible towards this approach without enhancing toxicity in general. Most of the strategies targeting apoptosis in glioblastomas presented here are in a pre-clinical stage of development, however, they all share the ultimative goal to improve the outcome for glioblastoma patients.
Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, CH-8091 Zurich, Switzerland. guenter.eisele@usz.ch
Günter
G
Eisele
Michael
M
Weller
D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016923:Cell Death; D053222:Fas Ligand Protein / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D053222:Fas Ligand Protein; D036341:Intercellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53