Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA; College of Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
Carle Illinois College of Medicine, University of Illinois Urbana Champaign, Champaign, IL, USA; Department of Neurosurgery, Carle Foundation Hospital, Urbana, IL, USA.
Pharmacol Res. 2024 Oct;208:107390. doi: 10.1016/j.phrs.2024.107390. Epub 2024 Sep 2.
Glioma is one of the most common central nervous system (CNS) cancers that can be found within the brain and the spinal cord. One of the pressing issues plaguing the development of therapeutics for glioma originates from the selective and semipermeable CNS membranes: the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). It is difficult to bypass these membranes and target the desired cancerous tissue because the purpose of the BBB and BSCB is to filter toxins and foreign material from invading CNS spaces. There are currently four varieties of Food and Drug Administration (FDA)-approved drug treatment for glioma; yet these therapies have limitations including, but not limited to, relatively low transmission through the BBB/BSCB, despite pharmacokinetic characteristics that allow them to cross the barriers. Steps must be taken to improve the development of novel and repurposed glioma treatments through the consideration of pharmacological profiles and innovative drug delivery techniques. This review addresses current FDA-approved glioma treatments' gaps, shortcomings, and challenges. We then outline how incorporating computational BBB/BSCB models and innovative drug delivery mechanisms will help motivate clinical advancements in glioma drug delivery. Ultimately, considering these attributes will improve the process of novel and repurposed drug development in glioma and the efficacy of glioma treatment.
神经胶质瘤是最常见的中枢神经系统 (CNS) 癌症之一，可以在大脑和脊髓中发现。困扰神经胶质瘤治疗发展的一个紧迫问题源于选择性和半透性 CNS 膜：血脑屏障 (BBB) 和血脊髓屏障 (BSCB)。由于 BBB 和 BSCB 的目的是过滤入侵 CNS 空间的毒素和异物，因此很难绕过这些膜并靶向所需的癌组织。目前有四种经美国食品和药物管理局 (FDA) 批准的用于治疗神经胶质瘤的药物；然而，这些疗法存在局限性，包括但不限于通过 BBB/BSCB 的相对低传输，尽管药代动力学特征允许它们穿过屏障。必须采取措施通过考虑药理学特征和创新的药物输送技术来改善新型和重新利用的神经胶质瘤治疗方法的开发。这篇综述讨论了目前 FDA 批准的神经胶质瘤治疗方法的差距、缺点和挑战。然后，我们概述了如何将计算 BBB/BSCB 模型和创新的药物输送机制纳入其中，以帮助推动神经胶质瘤药物输送的临床进展。最终，考虑到这些属性将改善神经胶质瘤中新型和重新利用药物开发的过程以及神经胶质瘤治疗的效果。
