Efficient Heat Shock Response Affects Hyperthermia-Induced Radiosensitization in a Tumor Spheroid Control Probability Assay

Hyperthermia (HT) combined with irradiation is a well-known concept to improve the curative potential of radiotherapy. Technological progress has opened new avenues for thermoradiotherapy, even recurrent head and neck squamous cell carcinomas (HNSCC). Preclinical evaluation radiosensitizing various HT regimens remains ethically, economically, technically challenging. One key objective our study was refine an advanced 3-D assay setup + RT research treatment testing. For first time, HT-induced radiosensitization systematically examined in two differently radioresponsive HNSCC spheroid models using unique vitro “curative” analytical endpoint control probability. We further investigated cellular stress response mechanisms underlying HT-related process aim unravel impact proteotoxic on overall radioresponse. disrupted proteome’s thermal stability, causing severe stress. It strongly enhanced radiation efficacy affected paramount survival signaling networks. Transcriptomics, q-PCR, western blotting data revealed that co-treatment critically triggers heat shock (HSR). Pre-treatment chemical chaperones intensified effect, thereby suppressing Hsp27 expression. Our suggest adversely by response. Hence, we propose inhibition particular proteins as targeting strategy outcome combinatorial RT.