Antiangiogenic therapy for glioblastoma: current status and future prospects.
Glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative proangiogenic signal transduction pathways are activated, leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma. However, future studies are warranted. Predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple proangiogenic pathways may prove effective.
Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts. tbatchelor@mgh.harvard.edu.
Tracy T
TT
Batchelor
Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
David A
DA
Reardon
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
John F
JF
de Groot
Neurooncology, University Clinic Heidelberg and German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany.
Wolfgang
W
Wick
Department of Neurology and Brain Tumor Center, University Hospital Zurich, Zurich, Switzerland.
Michael
M
Weller
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D003952:Diagnostic Imaging; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D015415:Biomarkers