Future directions in glioblastoma therapy.
The standard of care for both newly diagnosed and recurrent glioblastoma (GBM) patients has changed significantly in the past 10 years. Surgery followed by radiation and concurrent and adjuvant temozolomide is now the well-established standard treatment for newly diagnosed GBM. More recently, bevacizumab has become a mainstay of treatment for recurrent GBM. However, despite these advances and significant improvements in patient outcomes, the management and treatment of GBM patients remains a challenging and frustrating endeavor. Difficulties in interpretation of imaging changes after initial treatment, as well as the effects of antiangiogenic agents like bevacizumab on MRI characteristics, can make even the determination of disease progression complicated in multiple situations. Although a high percentage of patients benefit from antiangiogenic therapy in terms of radiographic response and progression-free survival, the effects of bevacizumab on prolonging overall survival remain controversial. Furthermore, tumor progression after treatment with antiangiogenic agents carries a particularly poor prognosis and there is a general lack of effective therapies for this group of patients. These limitations in terms of standard treatments contrast with a relative wealth of new information regarding the molecular underpinnings of GBM. Data from several large-scale efforts to molecularly profile GBM tumors including The Cancer Genome Atlas (TCGA) project have helped define specific molecular subtypes of GBM with distinct biology and clinical outcomes. These findings are helping to refine our understanding of the molecular heterogeneity and pathogenesis of these tumors and provide a basis for the future development of rational and targeted therapies for specific tumor subtypes.
From the Department of Neurosurgery and Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Howard
H
Colman