Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, APHP, Paris 5 University, Paris, France.
CarThera, Institut Du Cerveau et de La Moelle épinière (ICM), Paris, F-75013, France.
Cancer Lett. 2020 Jun 1;479:13-22. doi: 10.1016/j.canlet.2020.02.013. Epub 2020 Feb 27.
The treatment of primary brain tumors, especially malignant gliomas, remains challenging. The failure of most treatments for this disease is partially explained by the blood-brain barrier (BBB), which prevents circulating molecules from entering the brain parenchyma. Ultrasound-induced BBB disruption (US-BBBD) has recently emerged as a promising strategy to improve the delivery of therapeutic agents to brain tumors. A large body of preclinical studies has demonstrated that the association of low-intensity pulsed ultrasound with intravenous microbubbles can transiently open the BBB in a localized manner. The safety of this technique has been assessed in numerous preclinical studies in both small and large animal models. A large panel of therapeutic agents have been delivered to the brain in preclinical models, demonstrating both tumor control and increased survival. This technique has recently entered clinical trials with encouraging preliminary data. In this review, we describe the mechanisms and histological effects of US-BBBD and summarize the preclinical studies published to date. We furthermore provide an overview of the current clinical development and future potential of this promising technology.
原发性脑肿瘤的治疗，尤其是恶性神经胶质瘤的治疗，仍然具有挑战性。这种疾病的大多数治疗方法都失败了，部分原因是血脑屏障（BBB）的存在，它阻止了循环中的分子进入脑实质。超声诱导的血脑屏障破坏（US-BBBD）最近成为一种有前途的策略，可以改善治疗剂向脑肿瘤的输送。大量的临床前研究表明，低强度脉冲超声与静脉内微泡联合使用可以局部短暂地打开血脑屏障。这种技术的安全性已经在小型和大型动物模型的许多临床前研究中进行了评估。大量的治疗剂已经在临床前模型中被递送到大脑中，显示出肿瘤控制和提高存活率的效果。这项技术最近已经进入临床试验，并取得了令人鼓舞的初步数据。在这篇综述中，我们描述了 US-BBBD 的机制和组织学效应，并总结了迄今为止发表的临床前研究。我们还概述了这项有前途的技术的当前临床发展和未来潜力。
