Department of Biomedicine, Unit of Biochemistry, Faculty of Medicine, University of Porto, Al Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
Instituto de Investigação E Inovação Em Saúde (i3S), University of Porto, Porto, Portugal.
Cancer Chemother Pharmacol. 2021 Apr;87(4):447-464. doi: 10.1007/s00280-020-04218-6. Epub 2021 Jan 19.
Cancer cells are metabolically reprogrammed to support their high rates of proliferation, continuous growth, survival, invasion, metastasis, and resistance to cancer treatments. Among changes in cancer cell bioenergetics, the role of glutamine metabolism has been receiving increasing attention. Increased glutaminolysis in cancer cells is associated with increased expression of membrane transporters that mediate the cellular uptake of glutamine. ASCT2 (Alanine, Serine, Cysteine Transporter 2) is a Na-dependent transmembrane transporter overexpressed in cancer cells and considered to be the primary transporter for glutamine in these cells. The possibility of inhibiting ASCT2 for antineoplastic therapy is currently under investigation. In this article, we will present the pharmacological agents currently known to act on ASCT2, which have been attracting attention in antineoplastic therapy research. We will also address the impact of ASCT2 inhibition on the prognosis of some cancers. We conclude that ASCT2 inhibition and combination of ASCT2 inhibitors with other anti-tumor therapies may be a promising antineoplastic strategy. However, more research is needed in this area.
癌细胞的代谢被重新编程以支持其高增殖率、持续生长、存活、侵袭、转移和对癌症治疗的耐药性。在癌细胞生物能量变化中,谷氨酰胺代谢的作用越来越受到关注。癌细胞中谷氨酰胺分解代谢的增加与介导细胞摄取谷氨酰胺的膜转运体表达增加有关。ASCT2(丙氨酸、丝氨酸、半胱氨酸转运体 2)是一种在癌细胞中过度表达的 Na 依赖性跨膜转运体,被认为是这些细胞中谷氨酰胺的主要转运体。目前正在研究抑制 ASCT2 用于抗肿瘤治疗的可能性。在本文中,我们将介绍目前已知作用于 ASCT2 的药理学制剂,这些制剂在抗肿瘤治疗研究中引起了关注。我们还将讨论 ASCT2 抑制对某些癌症预后的影响。我们得出结论,ASCT2 抑制和 ASCT2 抑制剂与其他抗肿瘤疗法的联合可能是一种有前途的抗肿瘤策略。然而,这一领域还需要更多的研究。