Hyperthermia Treatment as a Promising Anti-Cancer Strategy: Therapeutic Targets, Perspective Mechanisms and Synergistic Combinations in Experimental Approaches

Abstract

Despite recent developments in diagnosis and treatment options, cancer remains one of the most critical threats to health. Several anti-cancer therapies have been identified, but further research is needed to provide more treatment options that are safe and effective for cancer. Hyperthermia (HT) is a promising treatment strategy for cancer because of its safety and cost-effectiveness. This review summarizes studies on the anti-cancer effects of HT and the detailed mechanisms. In addition, combination therapies with anti-cancer drugs or natural products that can effectively overcome the limitations of HT are reviewed because HT may trigger protective events, such as an increase of heat shock proteins (HSPs). In the 115 reports included, the mechanisms related to apoptosis, cell cycle, reactive oxygen species, mitochondrial membrane potential, DNA damage, transcription factors and HSPs were considered important. This review shows that HT is an effective inducer of apoptosis. Moreover, the limitations of HT may be overcome using combined therapy with anti-cancer drugs or natural products. Therefore, appropriate combinations of such agents with HT will exert maximal effects to treat cancer.

Injectable hydrogels for the delivery of nanomaterials for cancer combinatorial photothermal therapy

“…13,94,96 Such effects are non-reversible and ultimately lead to cell death by necrosis. 97,98 The cellular and molecular mechanisms prompted by these photothermally induced events have been extensively reviewed elsewhere. 99–103…”

In Vitro Effect of Herbal Medicines with Thermal Characteristics on Heat Sensitivity in Cancer Cells

“…For this experimental model of mild hyperthermia the temperatures 42°C and 43°C were selected [8]. Cancer cells were seeded in a 96-well plate at a density of 1.5 × 10 4 cells/well in 0.1 mL of media, followed by immersion in a temperature-controlled water bath (42°C or 43°C for mild hyperthermia and 37°C for normothermia) for 30 minutes.…”

“…Hyperthermia is a potential option for the treatment of cancer since it has less side effects than conventional medications and is cost-effective in light of its substantial therapeutic benefit, particularly when paired with other treatments [6,7]. It has been reported that hyperthermia alone may not be adequate to eradicate cancerous cells but in combination with natural products, the limitations of hyperthermia may be overcome [8]. Thermic stimulation causes apoptosis but also activates transcription factors important in tumor survival, causing tumor cells to proliferate more rapidly and develop resistance to anticancer drugs.…”

Combination of phototherapy with immune checkpoint blockade: Theory and practice in cancer

“…High temperatures can induce receptor interacting protein kinase (RIPK)-1, fas-associated death domain (FADD). And the upregulated RIPK1 and FADD in tumor cells can associate with caspase-8 to induce apoptosis (53)(54)(55)(56). ROS promotes activation of death receptor pathways by inhibiting the production of Bcl-2/Bcl-xL and upregulating the expression of apoptotic-related proteins Bax.…”