Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive malignancy with a poor prognosis, particularly when diagnosed at advanced stages. Despite progress in surgical, chemotherapeutic, and radiotherapeutic interventions, the five-year survival rate remains low due to high rates of recurrence and therapeutic resistance. This review explores recent advances in therapeutic strategies for HNSCC, focusing on targeted therapies, immunotherapy, and innovative drug delivery systems. Targeted therapies, such as EGFR inhibitors and PI3K/AKT/mTOR pathway inhibitors, offer promising options for overcoming HNSCC, though resistance challenges persist. Emerging treatments, including dual-target inhibitors and personalized therapeutic approaches, show potential in addressing these limitations. Immunotherapy, particularly PD-1/PD-L1 blockade, has achieved positive outcomes in a subset of patients, though overall response rates remain modest. Strategies aimed at enhancing immune responses, such as combination therapies and nanotechnology-based drug delivery systems, are actively being investigated to improve efficacy. This review also underscores the critical role of the tumor microenvironment and epithelial-mesenchymal transition (EMT) in HNSCC progression and therapeutic resistance. Novel approaches, including smart drug delivery systems utilizing nanotechnology and immune modulation, are opening new avenues for more personalized and effective treatments. Ongoing interdisciplinary research into molecular targets and advanced drug delivery techniques holds great promise for significantly improving patient outcomes in HNSCC.
Keywords: Drug delivery systems; HNSCC; Immunotherapy; Targeted therapy; Tumor microenvironment.
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