Kinesin superfamily proteins in head and neck cancer: Mechanisms, clinical implications, and therapeutic potential

Head and neck cancer, particularly head and neck squamous cell carcinoma (HNSCC), remains a substantial cause of cancer-related morbidity and mortality. Although surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy have improved disease management, the prognosis of patients with advanced or recurrent disease remains poor. Increasing evidence suggests that kinesin superfamily proteins (KIFs), microtubule-based molecular motors involved in intracellular transport and chromosome dynamics, have important roles in head and neck cancer. This review examines the current evidence on KIF dysregulation in head and neck cancer, with particular emphasis on their contributions to tumor biology, regulatory mechanisms, clinical relevance, and therapeutic potential. This narrative review examined peer-reviewed preclinical and clinical studies on KIF involvement in major features of head and neck cancer, including cell proliferation, invasion, metastasis, epithelial-to-mesenchymal transition (EMT), cancer stemness, cell-cycle progression, apoptosis, and treatment resistance. We also considered evidence on regulatory mechanisms, including non-coding RNAs, ubiquitin-mediated proteolysis, and N6-methyladenosine (m6A) modification, along with studies investigating KIFs as prognostic biomarkers or therapeutic targets. The available evidence supports an important role for several KIFs in head and neck cancer progression, particularly through effects on cell-cycle regulation, survival, migration, and oncogenic signaling. Nevertheless, KIF activity is not uniformly oncogenic. The effects of individual family members appear to depend on tumor subtype, anatomical site, molecular context, and human papillomavirus (HPV) status. In addition, the predominance of experimental studies and relatively small clinical cohorts limits the strength of current clinical evidence. Future studies should clarify the context-specific functions of individual KIFs using HPV- and subtype-stratified models and integrated transcriptomic, proteomic, and epigenetic approaches. Validation in clinically relevant models and larger, independent patient cohorts will be important for establishing their biomarker value. Selective kinesin inhibitors also warrant further investigation to determine whether these proteins can be effectively exploited for therapeutic intervention in head and neck cancer.