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Oxygenation of Solid Tumors in Animals and Patients

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Antiangiogenic Agents in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The biological effectiveness of low energy transfer (LET) ionizing radiation is in part related to the amount of oxygen present at the time of the energy deposit. This dose modifying role of oxygen (oxygen enhancement ratio) is principally caused by the indirect effect ofradiation on DNA (1,2). Hypoxic cells are present in rodent and xenografted human tumors, and it has been known for a long time that the absence ofoxygen in tumors is a factor ofresistance against ionizing radiation (3–5). More recently, it has been shown that the decrease in tumor oxygen tension could also be a factor ofresistance for treatment with some cytotoxic drugs (6–8), not only directly through the low-oxygen partial pressures, but indirectly through modifications in some gene expression by O2 and other environmental factors (vascularization, pH, metabolism, angiogenic factors, and so on) (9,10). In patients, tumors are known to contain hypoxic areas (11–14), and the local control of human solid tumors could be improved if a clinically relevant test was able to identify tumors that would benefit from radiosensitization (5). Oxygen availability is dependent on oxygen supply, which depends on many parameters: microvasculature, blood flow, tissue temperature, and pH (15,16). Tissue oxygenation will result directly from 02 availability, and from the respiration rate ofthe cells. For normal tissues, changes in oxygenation reflect variations in blood flow, and partial oxygen pressure (pO2) distribution has been evaluated as a function of hemoglobin concentration, temperature, pH, and so on (15). In tumors, tissue vascularization is qualitatively poor with shunts, vessel collapses, and high interstitial pressure. All these parameters may represent a potential therapeutic target (16–18).

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  1. Eric Lartigau
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  2. Marcelle Guichard
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  1. Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, USA

    Beverly A. Teicher

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Lartigau, E., Guichard, M. (1999). Oxygenation of Solid Tumors in Animals and Patients. In: Teicher, B.A. (eds) Antiangiogenic Agents in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-453-5_2

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  • DOI: https://doi.org/10.1007/978-1-59259-453-5_2

  • Publisher Name: Humana Press, Totowa, NJ

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