Target the Human Alanine/Serine/Cysteine Transporter 2(ASCT2): Achievement and Future for Novel Cancer Therapy

Glutamine metabolism, described as major energy and building blocks supply to cell growth, has gained great attention. Alanine-Serine-Cysteine Transporter (ASCT2), which belongs to solute carried (SLC) family transporters and is encoded by the SLC1A5 gene serves as a significant role for glutamine transport. Indeed, ASCT2 is often overexpressed in highly proliferative cancer cells to fulfill enhanced glutamine demand. So far, ASCT2 has been proved to be a significant target during the carcinogenesis process, and emerging evidence reveals that ASCT2 inhibitors can provide a benefit strategy for cancer therapy. Herein, we describe the structure of ASCT2, and summarize its related regulatory factors which are associated with antitumor activity. Moreover, this review article highlights the remarkable reform of discovery and development for ASCT2 inhibitors. On the basis of case studies, our perspectives for targeting ASCT2 and development of ASCT2 antagonist are discussed in the final part.

Keywords: 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, UCPH101(PubChem CID: 25223366); ASCT2; Benzyl-cysteine (PubChem CID: 101603455); Benzyl-serine (PubChem CID: 78457); Cancer; DTE (PubChem CID: 439352); Glutamine transporter; Inhibitors; L-4Cl proline-glycine (PubChem CID: 738019); L-γ-glutamyl-p-nitroanilide (GPNA, PubChem CID: 558754); V-9302 (PubChem CID:127035871); γ-2-fluorobenzyl proline (PubChem CID:2761966).