Research progress of BRD4 in head and neck squamous cell carcinoma: Therapeutic application of novel strategies and mechanisms

Bromodomain-containing protein 4 (BRD4) belongs to the bromodomain and extra-terminal domain (BET) protein family, which plays a crucial role in recognizing acetylated lysine residues in chromatin. The abnormal expression of BRD4 contributes to the development of various human malignant tumors, including head and neck squamous cell carcinoma (HNSCC). Recent studies have shown that BRD4 inhibition can effectively prevent the proliferation and growth of HNSCC. However, the specific role and mechanism of BRD4 in HNSCC are not yet fully clarified. This article will briefly summarize the critical role of BRD4 in the pathogenesis of HNSCC and discuss the potential clinical applications of targeting BRD4 in HNSCC therapy. We further inquiry the challenges and opportunities for HNSCC therapies based on BRD4 inhibition, including BRD4 inhibitor combination with conventional chemotherapy, radiotherapy, and immunotherapy, as well as new strategies of BRD4-targeting drugs and BRD4 proteolysis-targeting chimeras (PROTACs). Moreover, we will also offer outlook on the associated challenges and future directions of targeting BRD4 for the treatment of patients with HNSCC.