Abstract
Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Vaupel P, Mayer A, Höckel M (2004) Tumor hypoxia and malignant progression. Methods Enzymol 381:335–354
Vaupel P, Höckel M, Mayer A (2007) Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal 9:1221–1235
Vaupel P, Mayer A (2007) Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 26:225–239
Höckel M, Knoop C, Schlenger K et al (1993) Intratumoral pO2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 26:45–50
Höckel M, Schlenger K, Aral B et al (1996) Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56:4509–4515
Mayer A, Vaupel P (2013) Hypoxia, lactate accumulation, and acidosis: siblings or accomplices driving tumor progression and resistance to therapy? Adv Exp Med Biol 789:203–209
Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9:539–549
Brown JM (1979) Evidence for acutely hypoxic cells in mouse tumours, and a possible mechanism of reoxygenation. Br J Radiol 52:650–656
Chaplin DJ, Durand RE, Olive PL (1986) Acute hypoxia in tumors: implications for modifiers of radiation effects. Int J Radiat Oncol Biol Phys 12:1279–1282
Bayer C, Shi K, Astner ST et al (2011) Acute versus chronic hypoxia: why a simplified classification is simply not enough. Int J Radiat Oncol Biol Phys 80:965–968
Maftei CA, Bayer C, Shi K et al (2011) Quantitative assessment of hypoxia subtypes in microcirculatory supply units of malignant tumors using (immuno-)fluorescence techniques. Strahlenther Onkol 187:260–266
Matsumoto S, Yasui H, Mitchell JB et al (2010) Imaging cycling tumor hypoxia. Cancer Res 70:10019–10023
Bayer C, Vaupel P (2012) Acute versus chronic hypoxia in tumors: controversial data concerning time frames and biological consequences. Strahlenther Onkol 188:616–627
Aguilera A, Gomez-Gonzalez B (2008) Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet 9:204–217
Bindra RS, Crosby ME, Glazer PM (2007) Regulation of DNA repair in hypoxic cancer cells. Cancer Metastasis Rev 26:249–260
Talks KL, Turley H, Gatter KC et al (2000) The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol 157:411–421
Ratcliffe PJ (2007) HIF-1 and HIF-2: working alone or together in hypoxia? J Clin Invest 117:862–865
Acknowledgments
The authors thank Dr. Debra Kelleher for her valuable editorial help during preparation of this manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Dedicated to the memory of Dr. Britton Chance on the occasion of his 100th birthday (July 24, 2013), and remembering many exciting discussions on the inadequate and heterogeneous oxygenation of breast cancer.
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this paper
Cite this paper
Vaupel, P., Mayer, A. (2014). Hypoxia in Tumors: Pathogenesis-Related Classification, Characterization of Hypoxia Subtypes, and Associated Biological and Clinical Implications. In: Swartz, H.M., Harrison, D.K., Bruley, D.F. (eds) Oxygen Transport to Tissue XXXVI. Advances in Experimental Medicine and Biology, vol 812. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0620-8_3
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0620-8_3
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-0583-6
Online ISBN: 978-1-4939-0620-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)