Unravelling SLC7 family members in thyroid cancer and translational barriers

SLC7 family transporters are an important group of membrane proteins that facilitate the transport of different amino acids across the cell membrane. They have a crucial role in oncogenic signalling pathways, cellular metabolism, and redox balance. Previous literature had revealed the functions of SLC7 in breast, liver, prostate, and lung cancers, but the role of SLC7 family members in thyroid cancer remains unclear. Therefore, this review investigated the emerging roles of SLC7, the molecular mechanisms underlying thyroid cancer progression, and strategies to improve its therapeutic delivery. In thyroid cancer, mutations in SLC7 subunits could further dysregulate amino acid metabolism and activate the PI3K/AKT, mTORC1, and MAPK/ERK signalling pathways. The activation of oncogenic signals, such as MYC, ATF4, and HIF-1α, could further enhance the SLC7 expression by promoting tumour progression, angiogenesis, and cell proliferation, impairing T-cell activation, and inhibiting the activities of natural killer cells (NK) and cytotoxic T-lymphocytes (CTLs). They also served as potential therapeutic agents, and modulating them with novel immune checkpoint inhibitors, engineered CAR-T cells, and CRISPR-edited cells represents a promising strategy for thyroid cancer treatment. The present review could explore innovative insights into the molecular mechanisms of SLC7 in thyroid cancer development, identify the novel therapeutic targets, and improve their delivery for thyroid cancer immunotherapy.