ACRF Image X Institute, Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2050, Australia.
Monash Biomedical Imaging, Monash University, Clayton, VIC 3800, Australia.
J Control Release. 2022 May;345:443-463. doi: 10.1016/j.jconrel.2022.03.035. Epub 2022 Mar 23.
Survival outcomes for patients with glioblastoma multiforme (GBM) have remained poor for the past 15 years, reflecting a clear challenge in the development of more effective treatment strategies. The efficacy of systemic therapies for GBM is greatly limited by the presence of the blood-brain barrier (BBB), which prevents drug penetration and accumulation in regions of infiltrative tumour, as represented in a consistent portion of GBM lesions. Focused ultrasound (FUS) - a technique that uses low-frequency ultrasound waves to induce targeted temporary disruption of the BBB - promises to improve survival outcomes by enhancing drug delivery and accumulation to infiltrating tumour regions. In this review we discuss the current state of preclinical investigations using FUS to enhance delivery of systemic therapies to intracranial neoplasms. We highlight critical methodological inconsistencies that are hampering clinical translation of FUS and we provide guiding principles for future preclinical studies. Particularly, we focus our attention on the importance of the selection of clinically relevant animal models and to the standardization of methods for FUS delivery, which will be paramount to the successful clinical translation of this promising technology for treatment in GBM patients. We also discuss how preclinical FUS research can benefit the development of GBM immunotherapies.
过去 15 年来，多形性胶质母细胞瘤 (GBM) 患者的生存结果仍然很差，这反映出开发更有效的治疗策略面临明显挑战。由于血脑屏障 (BBB) 的存在，GBM 的全身治疗效果受到极大限制，该屏障阻止药物渗透和在浸润性肿瘤区域积累，GBM 病变的一部分就呈现出这种情况。聚焦超声 (FUS) - 一种使用低频超声波诱导 BBB 靶向性暂时破坏的技术 - 有望通过增强药物输送和在浸润性肿瘤区域的积累来提高生存结果。在这篇综述中，我们讨论了使用 FUS 增强颅内肿瘤系统治疗药物输送的当前临床前研究状况。我们强调了阻碍 FUS 临床转化的关键方法学不一致性，并为未来的临床前研究提供了指导原则。特别是，我们关注选择临床相关动物模型的重要性以及 FUS 输送方法的标准化，这对于将这项有前途的技术成功地转化为 GBM 患者的治疗方法至关重要。我们还讨论了临床前 FUS 研究如何有益于 GBM 免疫疗法的发展。
