Recent Clinical and Preclinical Advances in External Stimuli-Responsive Therapies for Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has long been one of the most prevalent cancers worldwide; even though treatments such as surgery, chemotherapy, radiotherapy and immunotherapy have been proven to benefit the patients and prolong their survival time, the overall five-year survival rate is still below 50%. Hence, the development of new therapies for better patient management is an urgent need. External stimuli-responsive therapies are emerging therapies with promising antitumor effects; therapies such as photodynamic (PDT) and photothermal therapies (PTT) have been tested clinically in late-stage HNSCC patients and have achieved promising outcomes, while the clinical translation of sonodynamic therapy (SDT), radiodynamic therapy (RDT), microwave dynamic/thermodynamic therapy, and magnetothermal/magnetodynamic therapy (MDT/MTT) still lag behind. In terms of preclinical studies, PDT and PTT are also the most extensively studied therapies. The designing of nanoparticles and combinatorial therapies of PDT and PTT can be referenced in designing other stimuli-responsive therapies in order to achieve better antitumor effects as well as less toxicity. In this review, we consolidate the advancements and limitations of various external stimuli-responsive therapies, as well as critically discuss the prospects of this type of therapies in HNSCC treatments.