Effects of hyperthermia as a mitigation strategy in DNA damage-based cancer therapies

Abstract

Utilization of thermal therapy (hyperthermia) is defined as the application of exogenous heat induction and represents a concept that is far from new as it goes back to ancient times when heat was used for treating various diseases, including malignancies. Such therapeutic strategy has gained even more popularity (over the last few decades) since various studies have shed light into understanding hyperthermia's underlying molecular mechanism(s) of action. In general, hyperthermia is applied as complementary (adjuvant) means in therapeutic protocols combining chemotherapy and/or irradiation both of which can induce irreversible cellular DNA damage. Furthermore, according to a number of in vitro, in vivo and clinical studies, hyperthermia has been shown to enhance the beneficial effects of DNA targeting therapeutic strategies by interfering with DNA repair response cascades. Therefore, the continuously growing evidence supporting hyperthermia's beneficial role in cancer treatment can also encourage its application as a DNA repair mitigation strategy. In this review article, we aim to provide detailed information on how hyperthermia acts on DNA damage and repair pathways and thus potentially contributing to various adjuvant therapeutic protocols relevant to more efficient cancer treatment strategies.

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells

“…Conversely, promotion of carcinogenesis and progression of tumors are both caused by defective apoptosis [6]. Apoptosis is an important mechanism of hyperthermia-induced cell death [7]. ROS generation is an upstream regulator of the mitochondria-mediated apoptosis pathway, which controls cell proliferation and cell death, cell migration, mitochondrial calcium loading, and other cellular functions [8] [9].…”

Case of successful treatment of subcutaneous granuloma annulare with local hyperthermia

“…Local hyperthermia has been successfully applied to treat cancer, and deep fungal, bacterial and viral skin infections. [3][4][5] To our knowledge, this is the first report to describe the clinical efficacy of hyperthermia in a patient with multiple SGA, and we presumed that hyperthermia possibly treated SGA by modulating the cellular immune response. In the context that the patient failed to respond to alternative therapies, local hyperthermia might be safe and effective as a second-line treatment option for patients who have exhausted more conventional therapies.…”

Overcoming multidrug resistance in cancer: Recent progress in nanotechnology and new horizons

“…Accumulating studies have reported that hyperthermia exerts multiple effects including direct killing of tumor cells via protein denaturation, DNA aggregation and cross‐linking, activating apoptotic pathways, changes in cell cycle regulatory signaling pathways, alterations in the tumor microenvironment, activation of heat shock proteins, induction of the immune response, alterations in blood flow, and oxygen and nutrient distribution at the tumor site . When BT‐474 cells are treated with magnetic nanoparticles and mitomycin‐C in the presence or absence of hyperthermia, it is reported that hyperthermia intensifies inhibitory effects of nanoparticles and mitomycin‐C on the expression levels of MDR‐associated proteins . Inactivation of drug detoxification mechanisms, increase in the drug uptake, induction of apoptosis, enhancement of drug cytotoxicity, and reduction in cell membrane localization of MDR proteins are other effects mediated by hyperthermia, which circumvent MDR in various cancers …”

“…81,82 When BT-474 cells are treated with magnetic nanoparticles and mitomycin-C in the presence or absence of hyperthermia, it is reported that hyperthermia intensifies inhibitory effects of nanoparticles and mitomycin-C on the expression levels of MDR-associated proteins. 83 Inactivation of drug detoxification mechanisms, increase in the drug uptake, induction of apoptosis, enhancement of drug cytotoxicity, and reduction in cell membrane localization of MDR proteins are other effects mediated by hyperthermia, which circumvent MDR in various cancers. 84 The application of ultrasound therapy to enhance therapeutic efficacy against cancer cells has been the subject of various clinical investigations.…”