%0 Journal Article
%T Antiangiogenic Therapy for Glioma
%A Valentina Cea
%A Carlo Sala
%A Chiara Verpelli
%J Journal of Signal Transduction
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/483040
%X Currently, antiangiogenic agents are routinely used for the treatment of patients with glioma. However, despite advances in pharmacological and surgical therapy, glioma remains an incurable disease. Indeed, the formation of an abnormal tumor vasculature and the invasion of glioma cells along neuronal tracts are proposed to comprise the major factors that are attributed to the therapeutic resistance of these tumors. The development of curative therapeutic modalities for the treatment of glioma requires further investigation of the molecular mechanisms regulating angiogenesis and invasion. In this review, we discuss the molecular characteristics of angiogenesis and invasion in human malignant glioma, we present several available drugs that are used or can potentially be utilized for the inhibition of angiogenesis in glioma, and we focus our attention on the key mediators of the molecular mechanisms underlying the resistance of glioma to antiangiogenic therapy. 1. Introduction Angiogenesis and tumor cell invasion play a critical role in glioma development and growth, even during the earliest phases [1]. Indeed, the formation of abnormal tumor vasculature and glioma cell invasion along white matter tracts are proposed to be the major causes of the therapeutic resistance of these tumors; thus, glioma remains a fatal disease despite advances in surgical and medical therapy. Glioma tumors are an example of highly vascularized tumors, which induce angiogenesis by upregulating vascular endothelial growth factor (VEGF) and its downstream pathways. Indeed, several molecular abnormalities have been described in glioma that promote angiogenesis, such as mutations and/or upregulation of PI3K/Akt and the VEGF receptor (VEGFR) in the glioma endothelium [2]. Interestingly, each of these signaling pathways involves alterations that can be therapeutically targeted [3]. Evaluation of drugs that target these pathways requires novel preclinical and clinical experimental trial design to define the optimal drug dose and delivery times to avoid toxicity during the first months of treatment [4, 5]. Furthermore, whether these agents can be used in combination with classical cytotoxic chemotherapy, what molecular markers can predict response, and whether they can be potentiated by such combinatorial treatments are important issues that remain to be explored. In this paper, we first discuss the molecular characteristics of angiogenesis and invasion in human malignant glioma. Secondly, we discuss the commercially available drugs that are currently used or might be potentially
%U http://www.hindawi.com/journals/jst/2012/483040/