Responses of Murine Tumors and Normal Tissues

Abstract

The data presented in Chapters 2 and 3 amply demonstrate that mild heating can kill cells and also that such heating accentuates the cytotoxicity of many anticancer agents. But it is a long way from experimental results on cell systems to the clinical use of hyperthermia. The next step in the usual hierarchy of experimental escalation is a demonstration that heat, either by itself or in cooperation with the more classical modalities, has beneficial effects against transplanted tumors in murine systems. By beneficial effects I do not only mean that tumors can be caused to regress or to be sterilized, but that this can be done without causing excessive damage to appropriate critical normal tissue. In this chapter I am going to provide evidence that demonstrates conclusively that some murine tumors can be eradicated by time-temperature profiles that cause only minimal normal tissue damage. The finding is not universal: other murine tumors appear to be more heat resistant, and their sterilization by heat alone can only be accomplished at the cost of considerable and perhaps excessive local tissue damage. I will also present data on combined heat-X-ray and heat-drug treatments; some of the heat-resistant tumors can be controlled effectively by these.