The heat shock response: Role in radiation biology and cancer therapy

Abstract

Since prehistoric times, elevated temperatures have been used to treat cancer in a variety of forms.In modern times (the last 40 years) efforts have concentrated on combining heat with otheranti-tumour modalities, principally ionizing radiation and some chemotherapeutic drugs. Despitethe emphasis on combined therapy, rodent data relating to heat sensitivity and thermal tolerancedevelopment assumed principal importance. These considerations suggested treating at 43°C asa target temperature and fractionation schemes emphasizing thermal tolerance avoidance.Concomitantly crucial data on heat-induced tumour reoxygenation and its temperature dependencewere largely ignored. In reality these were unrealistic and undesirable goals. The preponderance ofevidence now suggests that lower temperatures (40–42°C) administered more frequently, optimallyimmediately before and during each administration of ionizing radiation, are likely to yield optimalresults. Factoring in trimodality therapy and other combinations of chemotherapeutic drugs willrequire some modifications of such fractionation schemes.