Nasopharyngeal carcinoma (NPC) is a head and neck cancer with poor clinical outcomes and insufficient treatments in Southeast Asian populations. Although concurrent chemoradiotherapy has improved recovery rates of patients, poor overall survival and low efficacy are still critical problems. To improve the therapeutic efficacy, we focused on a tumor-associated protein called Annexin A2 (ANXA2). This review summarizes the mechanisms by which ANXA2 promotes cancer progression (e.g., proliferation, migration, the epithelial-mesenchymal transition, invasion, and cancer stem cell formation) and therapeutic resistance (e.g., radiotherapy, chemotherapy, and immunotherapy). These mechanisms gave us a deeper understanding of the molecular aspects of cancer progression, and further provided us with a great opportunity to overcome therapeutic resistance of NPC and other cancers with high ANXA2 expression by developing this prospective ANXA2-targeted therapy.
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