title: Signal transduction inhibitors and antiangiogenic therapies for malignant glioma.
abstract: Detailed characterization of the cancer genome in a large number of primary human glioblastomas has identified recurrent alterations that result in deregulation of signal transduction pathways and are "druggable" with a growing number of small molecule pharmaceuticals. While many of these compounds have shown clinical activity in other human cancers harboring similar genetic alterations, the clinical experience in glioblastoma has been disappointing thus far with only rare and transient radiographic responses. Our understanding of drug resistance is confounded by the uncertainty of drug delivery across the blood brain barrier and the limited knowledge to what extent the growth of these tumors depends on any particular signaling pathway. This uncertainty is, at least in part, due to shortcomings in the current approach to evaluate signal transduction inhibitors in glioma patients, including drug testing in molecularly unselected patient populations, limited documentation of drug penetration and target inhibition in tumor tissue, and use of radiographic response criteria that may not be optimal for the evaluation of these compounds. © 2011 Wiley-Liss, Inc.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, USA. mellingi@mskcc.org
authors.forename: Ingo K
authors.initials: IK
authors.lastname: Mellinghoff
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassman
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004791:Enzyme Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C512478:EGFR protein, human; D066246:ErbB Receptors