L-type amino acid transporters (LAT), encompassing LAT1 to LAT4, are localized on the cell membrane and intricately involved in cellular survival by facilitating the uptake of branched-chain amino acids. Recent revelations have shown that LAT1 is specifically expressed in malignant tumors and plays a significant role in their prognosis. Head and neck squamous cell carcinoma (HNSCC) ranks as the sixth most prevalent cancer globally, and although numerous treatments have been reported, the prognosis remains exceedingly grim. It has been documented that LAT1 is closely associated with cancer, yet the specifi cs of LAT1's function in HNSCC are largely unknown. This paper aims to shed light on the functions of LAT1-positive cells in HNSCC. LAT1-positive cells are characterized by enhanced spheroid formation, invasiveness, and migration capabilities, marking them as highly malignant. Furthermore, groups with high LAT1 expression exhibited treatment resistance and poorer prognosis compared to those with low expression.

The development of JPH203, an LAT1 inhibitor, has been conducted, yielding favorable outcomes in clinical trials for biliary cancer. Administration of JPH203 to HNSCC cells resulted in a signifi cant suppression of spheroid formation, invasiveness, and migration. Although further research is required, JPH203 has been suggested as an effective treatment for HNSCC, potentially offering a signifi cant improvement in prognosis.