Nucleolin as a Crucial Player in Head and Neck Cancer: Diagnostic and Therapeutic Perspectives.

Head and Neck Cancer (HNC) encompasses a diverse group of malignancies arising in the oral cavity, pharynx, larynx, and related structures. It represents a significant global health bur- den due to its high incidence, aggressive progression, and strong associations with environmental and viral risk factors like tobacco use and HPV infection. HNC, particularly squamous cell carcinoma, ranks as the seventh most common cancer worldwide. Despite the established role of these risk factors, the molecular mechanisms driving disease progression remain underexplored, especially in the context of specific biomarkers like Nucleolin (NCL). Nucleolin, a multifunctional protein, is pivotal in cancer progression, regulating cell proliferation, angiogenesis, and apoptosis. Data from The Cancer Genome Atlas (TCGA) reveal significant overexpression of NCL in HNC, particularly in advanced stages, correlating with poor prognosis and reduced patient survival. These findings highlight its potential as a diagnostic and therapeutic target. This review provides a fresh perspective on the underexplored potential of NCL as a therapeutic target in HPV-induced HNC and oral cancer. Emerging approaches, such as the AS1411 aptamer and F3 peptide, offer promising avenues for targeting NCL, paving the way for more effective, personalized cancer therapies.