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Hypoxia in Tumors: Pathogenesis-Related Classification, Characterization of Hypoxia Subtypes, and Associated Biological and Clinical Implications

Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 812)

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.

Keywords

Tumor hypoxia Acute hypoxia Chronic hypoxia Hypoxia subtypes Hypoxia classification 

Notes

Acknowledgments

The authors thank Dr. Debra Kelleher for her valuable editorial help during preparation of this manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  1. 1.Department of Radiooncology and RadiotherapyUniversity Medical CenterMainzGermany

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