Targeting Stem Cells with Hyperthermia: Translational Relevance in Cancer Patients

Abstract

<b><i>Background:</i></b> Tumor recurrences or metastases remain a major hurdle in improving overall cancer survival. In anticancer therapy, some patients inevitably develop chemo-/radiotherapy resistance at some point. Cancer stem cells are the driving force of tumorigenesis, recurrences, and metastases, contributing also to the failure of some cancer treatments. <b><i>Summary:</i></b> Emergent evidence suggests that stem cell diseases are at the base of human cancers, and tumor progression and chemo-/radiotherapy resistance may be dependent on just a small subpopulation of cancer stem cells. Hyperthermia can be a strong cancer treatment, especially when combined with radio- or chemotherapy. It is a relatively safe therapy, may kill or weaken tumor cells, and significantly increases the effectiveness of other treatments. However, these mechanisms remain largely unknown. A literature search was performed using PubMed including cited English publications. The search was last conducted in December 2019. Search phrases included “stem cells,” “hyperthermia,” “cancer,” and “therapy.” Abstracts, letters, editorials, and expert opinions were not considered for the drafting of the study. <b><i>Key Message:</i></b> Our goal was to focus on and to summarize different biological features of cancer stem cells and new therapeutic approaches using hyperthermia and its potential translation to human clinical trials.

Bevacizumab Plus FOLFOX-4 Combined With Deep Electro-Hyperthermia as First-line Therapy in Metastatic Colon Cancer: A Pilot Study

“…Finally, HT inhibits tumor angiogenesis through two different mechanisms. On the one hand, it directly damages endothelial cells because of the absorption of the electric field related thermal energy in the extracellular liquid, with a subsequent temperature gradient between the extra-and intracellular compartments, which threatens and/or destroys cancer cell membranes (67,68). On the other hand, it is well known that hypoxic tumor microenvironment stimulates the expression of hypoxiainducible factor-1 (HIF-1), which is the main VEGF inducer, the most powerful angiogenic factor.…”

Hyperthermia‐stimulated tonsil‐mesenchymal stromal cells suppress hematological cancer cells through downregulation of IL‐6

“…Its therapeutic potential has been demonstrated either alone or in combination with other standard treatments. [70][71][72] The limited number of studies have focused on the factors released from hyperthermia-stimulated MSCs, and few studies have demonstrated their antitumoral effects on solid cancers post determination of the potential of MSCs in cancer therapy. 72,73 Park et al 72 have reported that MSCs stimulated by hyperthermia could increase the effectiveness of chemotherapeutic drug therapy.…”

“…Hyperthermia is the process of raising the temperature on the tumor tissue up to 40−43°C, resulting in the induction of cancer cell death. Its therapeutic potential has been demonstrated either alone or in combination with other standard treatments 70–72 . The limited number of studies have focused on the factors released from hyperthermia‐stimulated MSCs, and few studies have demonstrated their antitumoral effects on solid cancers post determination of the potential of MSCs in cancer therapy 72,73 .…”

OTU deubiquitinase 7B facilitates the hyperthermia‐induced inhibition of lung cancer progression through enhancing Smac‐mediated mitochondrial dysfunction

“…Cellular responses to thermal stimuli range from activation of pathways that promote survival to programmed cell death to remove damaged cells. 26 When the thermal stimulus is strong enough, the cell activates the death signaling pathway. 27 During heat stress, cells rapidly upregulate the transcription and translation of HSP to protect cells from protein aggregation and degradation.…”