title: Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.
abstract: Tumor hypoxia is a hallmark of solid malignant tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of tumor hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of hypoxia within tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of tumor hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of tumor hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human tumor tissue.
authors.affiliation: Department of Radiation Oncology and Radiotherapy, Tumor Pathophysiology Section, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany. vaupel@uni-mainz.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Vaupel
authors.affiliation: Department of Radiation Oncology and Radiotherapy, Tumor Pathophysiology Section, University Medical Center, Langenbeckstr. 1, 55131, Mainz, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Mayer
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000378:metabolism*; D047368:Tumor Burden; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D010100:Oxygen
keywords: Hypoxia markers; Malignant progression; Multiparametric immunohistochemistry; Tumor hypoxia; Tumor hypoxia, detection; Tumor hypoxia, heterogeneities; Tumor hypoxia, subtypes