Abstract
Simple SummaryHyperthermia is a method to expose a tumor to elevated temperatures. Heating of the tumor promotes the effects of various treatment regimens that are based on chemo and radiotherapy. Several aspects, however, limit the efficacy of hyperthermia-based treatments. This review provides an overview of the effects and limitations of hyperthermia and discusses how current drawbacks of the therapy can potentially be counteracted by inhibiting the heat stress response—a mechanism that cells activate to defend themselves against hyperthermia.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.
Highlights
Hyperthermia (HT)—the exposure of malignant tissues to supraphysiological temperatures—is gaining popularity in clinical cancer treatment, and a wide range of HT-based strategies have been developed to achieve various clinical goals
We describe the various strategies by which cells detect heat stress and activate the transcriptional program known as the heat stress response
Treatments based on mild HT are applied to a widening range of cancer types
Summary
Hyperthermia (HT)—the exposure of malignant tissues to supraphysiological temperatures—is gaining popularity in clinical cancer treatment, and a wide range of HT-based strategies have been developed to achieve various clinical goals. Despite the clinical successes that have been achieved far, the efficacy of these treatments is limited by several factors including the emergence of thermotolerance—a phenotype of temporarily increased resistance to ongoing and subsequent heat exposure—in treated cells. Overcoming these limitations carries the promise of improving the clinical outcomes, irrespective of tumor or treatment type. Technical difficulties related to heating and temperature monitoring [4] temporarily prevented HT from competing with the gold standards in cancer treatment (i.e., surgery, chemotherapy, and radiotherapy), different forms of HT therapies are gaining popularity as standalone treatments, or in combination with other therapeutic agents
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