Gatekeeper or accomplice? That is the paradoxical role of the blood–brain barrier (BBB) in developing brain metastasis (BM). BM occurs when cancerous cells from primary cancer elsewhere in the body gain the ability to metastasize and invade the brain parenchyma despite the formidable defense of the BBB. These metastatic cells manipulate the BBB’s components, changing them from gatekeepers of the brain to accomplices that aid in their progression into the brain tissue. This dual role of the BBB—as both a protective system and a potential facilitator of metastatic cells—highlights its complexity. Even with metastasis therapy such as chemotherapy, BM usually recurs due to the BBB limiting the crossing of drugs via the efflux transporters; therefore, treatment efficacy is limited. The pathophysiology is also complex, and our understanding of the paradoxical interplay between the BBB components and metastatic cells still needs to be improved. However, advancements in clinical research are helping to bridge the knowledge gap, which is essential for developing effective metastasis therapy. By targeting the BBB neurovascular unit components such as the polarization of microglia, astrocytes, and pericytes, or by utilizing technological tools like focused ultrasound to transiently disrupt the BBB and therapeutic nanoparticles to improve drug delivery efficiency to BM tissue, we can better address this pathology. This narrative review delves into the latest literature to analyze the paradoxical role of the BBB components in the manifestation of BM and explores potential therapeutic avenues targeting the BBB–tumor cell interaction.
守护者还是帮凶？血脑屏障（BBB）在脑转移（BM）发展过程中扮演着这一矛盾角色。脑转移是指原发癌的癌细胞获得转移能力，突破血脑屏障的强大防御，侵入脑实质的过程。这些转移细胞通过调控血脑屏障的组成成分，使其从大脑的守护者转变为协助癌细胞侵入脑组织的帮凶。血脑屏障这种既作为保护系统又可能促进转移细胞入侵的双重角色，突显了其复杂性。即使采用化疗等转移治疗方法，由于血脑屏障通过外排转运蛋白限制药物通过，脑转移通常仍会复发，因此治疗效果有限。其病理生理机制同样复杂，我们对血脑屏障成分与转移细胞之间矛盾相互作用的理解仍有待深化。然而，临床研究的进展正在帮助弥合这一知识鸿沟，这对于开发有效的转移治疗方法至关重要。通过靶向血脑屏障神经血管单元成分（如小胶质细胞、星形胶质细胞和周细胞的极化），或利用聚焦超声等技术工具暂时破坏血脑屏障，以及采用治疗性纳米颗粒提高药物向脑转移组织的递送效率，我们能更好地应对这一病理过程。本叙述性综述通过梳理最新文献，深入分析血脑屏障成分在脑转移发生中的矛盾作用，并探索针对血脑屏障-肿瘤细胞相互作用的潜在治疗途径。
Deciphering the Blood–Brain Barrier Paradox in Brain Metastasis Development and Therapy
肿瘤(癌症)患者之家