Modulating the heat stress response to improve hyperthermia-based anticancer treatments

Cancer treatments based on mild hyperthermia (39–43◦C, HT) are applied to a widening range of cancer types, but several factors limit their efficacy and slow down more widespread adoption. These factors include difficulties in adequate heat delivery, a short therapeutic window and the acquisition of thermotolerance by cancer cells. Here, we explore the biological effects of HT, the cellular responses to these effects and their clinically-relevant consequences. We then identify the heat stress response—the cellular defense mechanism that detects and counteracts the effects of heat—as one of the major forces limiting the efficacy of HT-based therapies and propose targeting this mechanism as a potentially universal strategy for improving their efficacy.