Oxygen delivery to tumors.

Sensitization of hypoxic cells in tumors, by increasing their oxygen supply, has been attempted for at least 30 years. Only the use of hyperbaric oxygen has been shown unequivocally as a beneficial adjunct to radiotherapy; and even then, the number of sites sensitized is limited to head and neck and cervix. It is not clear whether this implies that all other tumors reoxygenate fully during treatment, or whether a better method would sensitize other sites. Nevertheless, the elimination of hypoxic cells is viewed by many as a worthy goal in radiobiology and many strategies have been tested in animal systems. These include: oxygen releasing chemicals, artificial oxygen carriers, inhibitors of oxygen consumption, blood flow modifiers, or the exploitation of tumor adaptation to altered oxygen availability. We must be aware that any procedure which improves tumor oxygenation will not only increase radiosensitivity, but will induce an adaptive response in the tumor such that, sensitization will be of limited duration. It is likely that in the apparent failure of measures to improve substantially the oxygen delivery to tumors, the elimination of most of the hypoxic cells, of the type accessible to them, may have been achieved. If, as has been suggested, there are two distinct types of hypoxic cells, a combination of more than one strategy may be necessary to achieve more substantial gains.