Mitotic Checkpoints and the Role of WEE1 Inhibition in Head and Neck Squamous Cell Carcinoma

Abstract

The WEE1 kinase family plays a crucial role in cell cycle regulation and DNA damage response pathways in malignant cells. Inhibition of WEE1 effectively overrides G2 cell cycle arrest and results in the accumulation of extensive DNA damage within dividing cells, potentiating mitotic catastrophe and cell death. As such, the development of WEE1 inhibitors as antineoplastic therapeutics has gained increasing interest in recent years. In particular, the role of WEE1 inhibitors for treatment of head and neck squamous cell carcinomas remains an area of active research with both preclinical and clinical studies investigating their use as both single-agent therapy and chemosensitizers when used in tandem with traditional chemotherapy, particularly in the context of TP53-mutant tumors. Here, we review the relevant available preclinical and clinical data on hand investigating the efficacy of WEE1 inhibitors for the treatment of head and neck cancers.