文章：

脑肿瘤和转移瘤中的血脑屏障和血肿瘤屏障

The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

原文发布日期：2019-10-10

DOI: 10.1038/s41568-019-0205-x

类型: Review Article

开放获取: 否

英文摘要：

For a blood-borne cancer therapeutic agent to be effective, it must cross the blood vessel wall to reach cancer cells in adequate quantities, and it must overcome the resistance conferred by the local microenvironment around cancer cells. The brain microenvironment can thwart the effectiveness of drugs against primary brain tumours as well as brain metastases. In this Review, we highlight the cellular and molecular components of the blood–brain barrier (BBB), a specialized neurovascular unit evolved to maintain brain homeostasis. Tumours are known to compromise the integrity of the BBB, resulting in a vasculature known as the blood–tumour barrier (BTB), which is highly heterogeneous and characterized by numerous distinct features, including non-uniform permeability and active efflux of molecules. We discuss the challenges posed by the BBB and BTB for drug delivery, how multiple cell types dictate BBB function and the role of the BTB in disease progression and treatment. Finally, we highlight emerging molecular, cellular and physical strategies to improve drug delivery across the BBB and BTB and discuss their impact on improving conventional as well as emerging treatments, such as immune checkpoint inhibitors and engineered T cells. A deeper understanding of the BBB and BTB through the application of single-cell sequencing and imaging techniques, and the development of biomarkers of BBB integrity along with systems biology approaches, should enable new personalized treatment strategies for primary brain malignancies and brain metastases.

摘要翻译： 

要使一种血液传播的癌症治疗剂有效，它必须穿过血管壁以足量到达癌细胞，并且必须克服癌细胞周围局部微环境所产生的抵抗力。大脑微环境会削弱药物对抗原发性脑肿瘤及脑转移瘤的效果。在本篇综述中，我们重点探讨了血脑屏障（BBB）的细胞和分子组成——这是一个特化的神经血管单元，其进化目的是维持大脑稳态。已知肿瘤会破坏血脑屏障的完整性，形成称为血瘤屏障（BTB）的血管系统，该系统具有高度异质性，并以诸多显著特征为标志，包括渗透性不均和分子的主动外排。我们讨论了血脑屏障和血瘤屏障给药物递送带来的挑战，多种细胞类型如何决定血脑屏障的功能，以及血瘤屏障在疾病进展和治疗中的作用。最后，我们重点介绍了新兴的分子、细胞和物理策略，以改善跨越血脑屏障和血瘤屏障的药物递送，并讨论了这些策略对改进传统疗法及新兴疗法（如免疫检查点抑制剂和工程化T细胞）的影响。通过应用单细胞测序和成像技术，开发血脑屏障完整性的生物标志物以及系统生物学方法，对血脑屏障和血瘤屏障的更深入理解应能为原发性脑恶性肿瘤和脑转移瘤提供新的个性化治疗策略。

原文链接：

The blood–brain barrier and blood–tumour barrier in brain tumours and metastases