Hyaluronan and the Interaction Between CD44 and Epidermal Growth Factor Receptor in Oncogenic Signaling and Chemotherapy Resistance in Head and Neck Cancer

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Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide.1 Patients with advanced-stage HNSCC continue to have poor 5-year survival rates (0%-40%), which have not significantly improved in the last 30 years. Understanding the mechanisms underlying HNSCC tumor progression and resistance to standard treatment are critical to improving outcomes for patients with this disease. Tumor progression (ie, tumor invasion, migration, and metastasis) is determined by both genetic mutations and the tumor's microenvironment, including the interaction between tumor cells and extracellular matrix molecules. Tumor drug resistance involves multiple mechanisms, including reduced drug accumulation, decreased apoptosis, alterations in drug target, and increased DNA damage repair. The interaction between tumor cells and their microenvironment can lead to the activation of oncogenic signaling pathways that promote both cancer progression and drug resistance.