Hypoxia in the tumorigenesis of gliomas and as a potential target for therapeutic measures.
In this article, the author provides a brief description of the role of hypoxia in the tumorigenesis of gliomas and suggests potential ways of exploiting this role to design treatment modalities. Tumor hypoxia predicts the likelihood of metastases, tumor recurrence, resistance to chemotherapy and radiation therapy, invasive potential, and decreased patient survival for many human malignancies. Various methods of measurement of tumor hypoxia are discussed, including direct measurement and imaging methods. The role of hypoxia-responsive molecules, especially hypoxia-inducible factor-1 (HIF-1), in glioma tumorigenesis is explored. Treatment modalities regulated by hypoxia are proposed and some potential strategies reviewed. The progression of a low-grade astrocytoma to a glioblastoma multiforme may be mediated by hypoxia-induced phenotypic changes and subsequent clonal selection of cells that overexpress hypoxia-responsive molecules, such as HIF-1. In this model, intratumoral hypoxia causes genetic changes that produce a microenvironment that selects for cells of a more aggressive phenotype.
Jensen
Randy L
RL
Department of Neurosurgery, University of Utah, Salt Lake City, Utah 84132, USA. randy.jensen@hsc.utah.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic
D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit