Targeting fibroblast growth factor receptor (FGFR) with inhibitors in head and neck cancers: Their roles, mechanisms and challenges

Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive type of cancer with significant rates of morbidity and mortality. Traditional treatment options, including radiotherapy, chemotherapy, and surgery, are widely used, but their effectiveness can be uncertain. As research in cancer therapies evolves, molecular-targeted therapies are increasingly recognized as promising alternatives for managing malignant tumors. Fibroblast growth factor receptors (FGFRs) have been shown to be one of the essential components in the pathways in the progression of HNSCC. This review aims to summarize and discuss the structure, functions, signaling pathways, abnormal alterations of FGFRs, and their roles in tumorigenesis and development. We have accumulated information from in vitro, in vivo, and clinical studies regarding FGFR inhibitors in HNSCC. However, the efficacy of FGFR inhibitors as a cancer therapy is limited, which may be due to the resistance to FGFR inhibitors. In this review we also discuss the potential mechanisms of FGFR inhibitor resistance in HNSCC. By enriching our understanding of the treatment with and resistance of FGFR inhibitors in HNSCC, researchers may unveil new therapeutic targets or strategies to enhance the efficacy of FGFR inhibitors in this context.