Brito Emanuella M, Baker Emma M, Ahye Nicholas M, Lieber Bryan A, Hettiarachchi Sajini, Hollweg Maria J Moreno, Safar Sabrin B, Vanni Steven, Graham Regina M
Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, 3300 S. University Drive, Fort Lauderdale, FL, 33328, USA.
Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, 3300 S. University Drive, Fort Lauderdale, FL, 33328, USA.
Mol Diagn Ther. 2025 Aug 22. doi: 10.1007/s40291-025-00810-9.
Glioblastoma (GBM) is an aggressive primary brain tumor with a median survival of 14-15 months even with standard multimodality treatments. The effectiveness of surgical resection, chemotherapy, and radiation therapy are limited by resistance mechanisms including tumor heterogeneity, immunosuppression, presence of stem-like cells, and inhibited drug delivery due to the blood-brain barrier (BBB). The BBB is composed of endothelial cells with tight junctions and selective transport systems, which prevent drug delivery to the tumor at therapeutic levels. Amino acid (AA) transporters have emerged as promising therapeutic targets for overcoming these limitations and enhancing GBM treatment. This review highlights the role of AA transporters in GBM, emphasizing their potential in enhancing targeted therapy, diagnosis, and disease monitoring. We summarize and discuss the 22 AA transporters which are upregulated in GBM, as well as those that demonstrate prognostic correlation. Among these, LAT1 (SLC7A5) has garnered the most attention for its role in drug delivery and imaging, while other transporters exhibit potential as diagnostic and therapeutic targets. Furthermore, nanoparticle technology has emerged as an innovative strategy to enhance targeted therapy through AA transporters. They can enable extended drug circulation, enhanced BBB penetration, and target-specific localization, offering synergistic therapeutic effects. This review emphasizes the importance of AA transporters as multifaceted tools for improving GBM treatment outcomes and the potential of combining AA transporter-targeted therapies with emerging technologies to address the limitations of current GBM management strategies.
胶质母细胞瘤（GBM）是一种侵袭性原发性脑肿瘤，即使采用标准的多模式治疗，其平均生存期也仅为14 - 15个月。手术切除、化疗和放射治疗的有效性受到多种耐药机制的限制，包括肿瘤异质性、免疫抑制、干细胞样细胞的存在以及血脑屏障（BBB）导致的药物递送受阻。血脑屏障由具有紧密连接和选择性转运系统的内皮细胞组成，这会阻碍治疗水平的药物递送至肿瘤。氨基酸（AA）转运体已成为克服这些限制并增强GBM治疗效果的有前景的治疗靶点。本综述重点介绍了AA转运体在GBM中的作用，强调了它们在增强靶向治疗、诊断和疾病监测方面的潜力。我们总结并讨论了在GBM中上调的22种AA转运体，以及那些与预后相关的转运体。其中，LAT1（SLC7A5）因其在药物递送和成像中的作用而备受关注，而其他转运体也展现出作为诊断和治疗靶点的潜力。此外，纳米颗粒技术已成为一种创新策略，可通过AA转运体增强靶向治疗。它们能够实现药物的延长循环、增强血脑屏障穿透以及靶向特异性定位，从而提供协同治疗效果。本综述强调了AA转运体作为改善GBM治疗结果的多方面工具的重要性，以及将AA转运体靶向治疗与新兴技术相结合以解决当前GBM管理策略局限性的潜力。
