Year: 2011
Type: article
Abstract: Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor.Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth factor (VEGF), and generates blood vessels with distinctive features.The outcome for patients with recurrent glioblastoma is poor because of ineffective therapies.However, recent encouraging rates of radiographic response and progression-free survival, and adequate safety, led the FDA to grant accelerated approval of bevacizumab, a humanized monoclonal antibody against VEGF, for the treatment of recurrent glioblastoma in May 2009.These results have triggered significant interest in additional antiangiogenic agents and therapeutic strategies for patients with both recurrent and newly diagnosed glioblastoma.Given the potent antiperme-ability effect of VEGF inhibitors, the Radiologic Assessment in Neuro-Oncology (RANO) criteria were recently implemented to better assess response among patients with glioblastoma.Although bevacizumab improves survival and quality of life, eventual tumor progression is the norm.Better understanding of resistance mechanisms to VEGF inhibitors and identification of effective therapy after bevacizumab progression are currently a critical need for patients with glioblastoma.(JNCCN 2011;9:414-427) Malignant gliomas, including the most common subtype of glioblastoma, are rapidly growing destructive tumors that extensively invade locally but rarely metastasize.The current standard of care, including maximum safe resection followed by radiation therapy and temozolomide chemotherapy, achieves median progressionfree and overall survivals of only 6.9 and 14.7 months, respectively.1 After progression, salvage therapies have historically achieved radiographic response and 6-month progression-free survival rates of 5% to 15%, respectively. [2][3]3][4] Several factors contribute to poor treatment response, including frequent de novo and acquired resistance, heterogeneity across and within tumors, complex and redundant intracellular pathways regulating proliferation and survival, and restricted central nervous system (CNS) delivery because of the blood-brain barrier and high interstitial peritumoral pressures.5,6 Given this background, recent clinical studies have shown substantive radiographic responses and improved progression-free survival with bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), 7 among patients with recurrent malignant glioma.[8][9][10][11] However, initial enthusiasm has
Institutions: Duke University, Duke Medical Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1845986149