Mechanisms of Resistance to Chemotherapy in Hypopharyngeal Carcinoma

Hypopharyngeal carcinoma (HPC) represents the most prognostically unfavorable subtype among head and neck malignancies. Platinum-based neoadjuvant chemotherapy serves as a critical therapeutic approach for improving outcomes in hypopharyngeal carcinoma; however, its efficacy remains suboptimal due to the high incidence of chemoresistance. Current research on chemoresistance has primarily focused on head and neck squamous cell carcinoma (HNSCC), yet significant heterogeneity exists between hypopharyngeal carcinoma and other head and neck tumors, limiting the direct applicability of broader HNSCC research findings to hypopharyngeal carcinoma. This review systematically summarizes recent advances in understanding the mechanisms underlying chemoresistance in hypopharyngeal carcinoma, with emphasis on the comprehensive elucidation of key mechanisms, including apoptosis evasion, enhanced DNA damage repair, augmented autophagy, and increased drug efflux. Moreover, three noteworthy special scenarios involving cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), and cancer-associated fibroblasts (CAFs) are discussed. These entities not only intrinsically participate in multiple chemoresistance mechanisms but also interact synergistically, thereby further exacerbating chemoresistance in hypopharyngeal carcinoma.