Angiogenesis and gliomas: current issues and development of surrogate markers.
Despite significant improvements, current therapies have yet to cure infiltrative gliomas. Glioma progression is strongly dependent on the development of a new vascular network that occurs primarily by angiogenesis. Hypoxia and genetic anomalies within a glioma trigger the angiogenic switch, thus upregulating angiogenic factors and downregulating antiangiogenic factors. The main factors indicative of angiogenesis are now well known, and more recently, differences based on grade and subtype have been reported. New data also indicate a potential role for postnatal vasculogenesis with bone marrow endothelial progenitors in addition to angiogenesis in tumor vascular development. All of these factors may have therapeutic implications. Antiangiogenic therapies are presently being developed; more than 80 trials are ongoing. Initial results indicate that epidermal growth factor receptor inhibitors, anti-metalloproteases, and thalidomide do not demonstrate strong anti-tumor activity. Thus, antiangiogenic agents combined with conventional therapies and second-generation antiangiogenic drugs for targeting multiple molecular pathways are presently being tested. Clinical experience also demonstrates the failure of conventional imaging to monitor these new approaches accurately. New advances in the design of surrogate markers for angiogenesis have been reported for both magnetic resonance and molecular imaging techniques. This article summarizes the mechanisms of the angiogenic switch based on tumor grade and subtype, reviews completed and ongoing clinical trials, and details the present and the future of surrogate markers for angiogenesis in gliomas.
Jouanneau
Emmanuel
E
Neurosurgical Department, Neurological Hospital Pierre Wertheimer, University Claude Bernard Lyon 1, Lyon, France. emmanuel.jouanneau@chu-lyon.fr
D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D015415:Biomarkers