Calcium Signaling Pathways in Head and Neck Squamous Cell Carcinoma Therapy: A Review

ABSTRACT Calcium ion (Ca 2+ ) is a crucial secondary messenger in cells and participates in multiple physiological activities, during which various calcium regulatory proteins regulate the Ca 2+ homeostasis. It has been verified that calcium signaling differs significantly between tumor and normal cells. Additionally, the heterogeneity in calcium signaling is found across head and neck squamous cell carcinoma (HNSCC) with different pathological subtypes and infection status of human papillomavirus. The abnormality of calcium signaling is related to the initiation, progression, therapeutic response, and clinical prognosis of HNSCC. Moreover, the calcium signaling plays a vital role in regulating the tumor microenvironment, which is closely related to the tumor cell and shares constant interaction with it, by metabolic reprogramming and immunosuppressive effects. Understanding the changes in calcium signaling may provide a potential target for the treatment of HNSCC.