Title: Hypoxia and the Malignant Glioma Microenvironment: Regulation and Implications for Therapy
VOLUME: 2 ISSUE: 3
Author(s):L. Oliver, C. Olivier, F. B. Marhuenda, M. Campone and F. M. Vallette
Affiliation:Institut de Recherche Therapeutique de l'Universite de Nantes, CRCNA INSERM UMR892 /Universite de Nantes, Equipe 9, 8 Quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.
Keywords:Apoptosis, hypoxia, glioma
Abstract: Glioblastoma Multiforme (GBM) tumors are the most common type of brain tumors. These tumors are in general very malignant and can be characterized as rapidly progressive astrocytomas. The pathological characteristics of these tumors are exemplified by an active invasiveness, necrosis and a specialized form of angiogenesis, known as microvascular hyperplasia. These pathological features are thought to be due to tissue hypoxia. Cells that are under hypoxic stress can either develop an adaptive response that includes increasing the rate of glycolysis and angiogenesis or undergo cell death by promoting apoptosis and/or necrosis. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducing factors (HIF), which are essential for the regulation of the expression of a large number of hypoxia-responsive genes. The hypothesis that tumor hypoxia would facilitate the likelihood of metastases, tumor recurrence, resistance to chemotherapy and radiotherapy and the invasive potential; all of which culminate in a decrease in patient survival. In this review we will summarize the role of hypoxia in GBM with regard to drug therapy and toxicity and attempt to describe the possible interactions between hypoxia and apoptosis.
