Encountering and Advancing Through Antiangiogenesis Therapy for Gliomas

Vanesa      Martin; Dan      Liu; Candelaria      Gomez-Manzano

Abstract

Malignant gliomas, the most common subtype of primary brain tumor, are aggressive, highly invasive, and neurologically destructive. First-line treatment of gliomas consists of surgery and radiotherapy, followed by chemotherapy with temozolomide. However, even with this strong regimen, the prognosis of patients with the most malignant variant, glioblastoma multiforme is poor. Because of the lack of effective treatments and the high vascularity that characterizes these tumors, antiangiogenic therapy of gliomas is being studied. This approach is supported by encouraging preclinical data in both in vitro and in vivo models. Clinical studies have shown that these agents do not cause high toxicity; and due to the effect they exert on vessel permeability, patients can avoid the use of corticosteroids and their accompanying adverse. Moreover, in studies of these agents, we have observed improvements in several parameters normally used to measure therapy response. However, whether these parameters are reliable for understanding and measuring the anticancer effect of antiangiogenic molecules is unknown. In addition, resistance to angiogenic therapy is already evident, and in studies performed in animal models, this resistance was associated with the appearance of more invasive phenotypes. These models give us the opportunity to further understand what causes therapy resistance and will allow us to test new combination therapies. Future studies are directed to understand if it is possible to target not only the bulk of the tumor but also the putative tumor niche composed of tumor cells, vessels, and stroma.

Keywords: Brain tumor, angiogenesis, cancer stem cell, antibody, tyrosine kinase inhibitor

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