Can Tumor Oxygenation be Improved by Reducing Cellular Oxygen Consumption?

Abstract

Tumor hypoxia, which can be found in many experimental and human tumors is an important factor influencing the therapeutic efficacy of standard radiotherapy, O₂-dependent chemotherapy and photodynamic therapy (Hall, 1994) and might be responsible for the development of aggressive tumor cell subpopulations (Graeber et al., 1996). Since this oxygen deficiency results from a disparity between O₂ supply to the tumor tissue and the oxygen demand of the cells, several attempts have been undertaken to improve tumor oxygenation primarily by increasing the arterial oxygen supply. The O₂ supply to the tumor cells can be improved by (a) increasing the arterial O₂ content (by breathing hyperoxic gases under normobaric or hyperbaric conditions, or by correcting tumor anemia); (b) improving tumor perfusion or increasing its uniformity; (c) enhancing oxygen release from blood by shifting the O₂-hemoglobin dissociation curve. However, theoretical studies by Secomb et al. (1995) using a comprehensive model of the tumor microcirculation (Secomb et al., 1993) postulated that tumor oxygenation could be improved much more effectively by reducing the oxygen consumption of the tumor cells. A reduction of 30% has been predicted to be necessary if tumor hypoxia is to be completely eradicated.

Supported by the Dr.med.h.c. Erwin Braun Foundation, Basel (Grant 5.5.6).