Advances in treating glioblastoma

Abstract

Glioblastoma is the most common and most aggressive primary brain tumor in adults. Optimized standard treatment only confers a modest improvement in progression and overall survival, underscoring the pressing need for the development of novel therapies. Our understanding of glioblastoma (a molecularly heterogeneous disorder) has been accelerated in the setting of large scale genomic analyses, lending insight into potential actionable targets. Antiangiogenic therapies have been used in the treatment of glioblastoma, and our understanding of the means to optimize the role of these agents is continuing to evolve. Recently, immunotherapy has garnered increasing attention as a therapeutic approach in the treatment of gliomas. Promising novel approaches are under active development in the treatment of glioblastoma.

Figure 1.. Graphical summary of key molecular and biologic characteristics of glioblastoma subgroups

A simplified schematic representation of key genetic and epigenetic findings in six glioblastoma subgroups as identified by methylation profiling and correlations with clinical patient data. Permission obtained from Elsevier publishing group. Cancer Cell, 2012. 22(4): p. 425-37. Abbreviations: CHOP, CpG hypomethylator phenotype; CIMP, CpG island methylator phenotype; EGFR, epidermal growth factor receptor; IDH, isocitrate dehydrogenase; PDGFRA, platelet derived growth factor receptor; RTK, receptor tyrosine kinase.

Figure 2.. Axial magnetic resonance (MR) images in a patient with recurrent glioblastoma

(A) Postcontrast MRI demonstrating an enhancing focus of disease adjacent to the right frontal horn. (B) Postcontrast MRI obtained 6 weeks following initiation of single agent bevacizumab demonstrating an interval reduction in contrast enhancing disease. (C) Fluid attenuated inversion recovery (FLAIR) sequence of the same patient at the same point in time as image (A) revealing subtle FLAIR hyperintensity adjacent to the anterior horns of the lateral ventricles. (D) FLAIR sequence obtained 6 weeks following initiation of single agent bevacizumab revealing interval evolution of confluent FLAIR signal changes adjacent to the right frontal horn consistent with non-enhancing disease progression. Abbreviations: FLAIR, fluid attenuated inversion recovery; MRI, magnetic resonance imaging.