Enhanced chemical cytotoxicity via hyperthermia

Enhanced chemical cytotoxicity via hyperthermia refers to a cancer treatment approach where mild hyperthermia (elevated temperatures of 39-45°C) is combined with chemotherapy to amplify tumor cell killing, rather than targeting a specific molecule. Hyperthermia exerts direct cytotoxic effects through mechanisms like protein denaturation, chromatin alterations, mitochondrial cristae degeneration, and induction of apoptosis or necrosis, particularly above 43°C. It synergizes with drugs by increasing tumor perfusion, membrane permeability, intracellular drug uptake, and inhibiting DNA repair, as shown in vitro with agents like epirubicin, mitomycin C, gemcitabine, and EO9 against bladder cancer cell lines. This modality exploits cancer cells' heat sensitivity, enhancing oxidative stress and immune responses like NK-cell lysis, while nanoparticles enable targeted local heating via magnetic fields, light, or ultrasound. Clinically, it improves outcomes in combination with radiation or chemo for various cancers (e.g., NSCLC, sarcoma, glioma), though thermotolerance and heterogeneous tumor responses limit standalone use. No single receptor or enzyme is implicated; it's a biophysical process studied since the 1970s for thermal chemosensitization.

No target-specific MOA; hyperthermia induces protein denaturation, chromatin changes, mitochondrial damage, ROS production, apoptosis/necrosis, and increases drug permeability/uptake.