New advances into cisplatin resistance in head and neck squamous carcinoma: Mechanisms and therapeutic aspects

Head and neck squamous cell carcinoma (HNSCC) arises from the interplay of multiple factors, such as smoking, alcohol consumption, and viral infections. Cisplatin-based concurrent radiotherapy regimens represent the first-line treatment for advanced HNSCC cases. However, cisplatin resistance significantly contributes to poor prognoses in HNSCC patients, making it crucial to unravel the underlying mechanisms to overcome this resistance. The complexity of cisplatin resistance in HNSCC involves cancer stem cells, autophagy, epithelial-mesenchymal transition, drug efflux, and metabolic reprogramming. Recent advances in nanodrug delivery systems, combined with existing small-molecule inhibitors and innovative genetic technologies, have opened new therapeutic avenues for addressing cisplatin resistance in HNSCC. This review systematically summarizes research progress from the past five years on cisplatin resistance in HNSCC, with a particular focus on the roles of cancer stem cells and autophagy. Additionally, potential future treatment strategies to overcome cisplatin resistance are discussed, including the targeting of cancer stem cells or autophagy through nanoparticle-based drug delivery systems. Furthermore, the review highlights the prospects and challenges associated with nanodelivery platforms in addressing cisplatin resistance in HNSCC.