Recent advances in ASCT2 inhibitors: ligand design and therapeutic applications.

"Glutamine addiction" is a hallmark metabolic feature of many cancer cells. Driven by the "Warburg effect," tumor cells exhibit an increased reliance on glutamine uptake and metabolism to sustain rapid proliferation and survival. As such, precise modulation of glutamine metabolic pathways has emerged as a promising strategy for cancer therapy. Alanine - serine - cysteine transporter 2 (ASCT2), a key glutamine transporter, is frequently overexpressed in a variety of cancer cells, facilitating elevated glutamine influx to meet the metabolic demands of malignant cells. Accordingly, pharmacological inhibition of ASCT2 represents an attractive approach to reduce intracellular glutamine availability and suppress tumor cell growth. This review provides a comprehensive overview of ASCT2, including its structural and functional characteristics, recent progress in small-molecule inhibitor development, and the potential for future therapeutic applications.