[show abstract][hide abstract] ABSTRACT: Glioblastoma is the most common primary brain tumor with a relatively poor prognosis. This article reviews the current standard therapy and discusses new developments in treatment of this disease. Surgical resection followed by radiation and chemotherapy has proven to be the most effective initial therapy. Recent advancement in molecular targeted therapies has led to the Food and Drug Administration (FDA) approval of bevacizumab in the setting of recurrent glioblastoma. The molecular pathways of glioblastoma growth are highlighted in this review. While numerous molecular targets are currently being intensely investigated, vascular endothelial growth factor (VEGF) receptor targeted therapy has been the only one to have shown clinical effect. The role of bevacizumab in this context provides a dynamic breakthrough in cancer therapy. Clinical trials have demonstrated significantly increased overall survival and six month progression free survival (PFS) in recurrent glioblastoma treated with bevacizumab alone or in combination with irinotecan. The use of this agent has also dramatically changed the imaging characteristics of glioblastoma. The anti-angiogenesis effects of bevacizumab have complicated the criterion for determining tumor growth. This may lead to redefinition of progressive disease based on non-invasive monitoring.
Pharmacogenomics and Personalized Medicine 01/2010; 3:79-85.
[show abstract][hide abstract] ABSTRACT: Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving approximately 35 significant events, including 16-18 broad events near chromosome-arm size and 16-21 focal events. Approximately half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have properties different from those with overlapping focalEGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome.
Proceedings of the National Academy of Sciences 01/2008; 104(50):20007-12. · 9.74 Impact Factor