Thermal enhancement of chemotherapeutic cytotoxicity

Thermal enhancement of chemotherapeutic cytotoxicity refers to the clinical and experimental finding that raising the temperature of tumor tissues—typically through hyperthermia (40–45 °C)—can significantly increase the effectiveness of chemotherapeutic drugs against cancer cells[1][2][3][5][7][9]. This enhancement results from several mechanisms, including inhibition of DNA repair, increased blood flow and vascular permeability (facilitating drug delivery and uptake), modulation of the tumor microenvironment, and direct cytotoxic effects at higher temperatures. Hyperthermia may also induce immune stimulation, further contributing to anti-tumor activity[1][9]. This strategy does not correspond to a unique molecular target or receptor but is instead a process applied in combination with other anti-cancer modalities such as chemotherapy, radiotherapy, and immunotherapy. As such, it cannot be treated as a canonical drug target for the purposes of drug discovery or biomarker identification.

Other names

Thermal enhancement of chemotherapyHyperthermia-mediated chemosensitizationChemotherapy thermal potentiationThermal sensitization of chemotherapy

Increased DNA damage in tumor cells when combined with chemotherapeutics; Inhibition of DNA repair mechanisms; Enhanced drug delivery into tumor tissues by increasing blood flow and vascular permeability; Improved cellular uptake of chemotherapeutic agents; Disruption of tumor microenvironment, including pH changes and increased immune activation; Induction of immunogenic cell death through release of DAMPs, HSPs, and cytokines; Direct cytotoxic effect via protein denaturation and mitochondrial dysfunction at higher temperatures.