Huang Rui, Boltze Johannes, Li Shen
Department of Neurology, Dalian Municipal Central Hospital Affiliated With Dalian Medical University, Dalian, China.
School of Life Sciences, University of Warwick, Coventry, United Kingdom.
Front Oncol. 2020 Aug 26;10:1443. doi: 10.3389/fonc.2020.01443. eCollection 2020.
Conventional treatments for brain tumors relying on surgery, radiation, and systemic chemotherapy are often associated with high recurrence and poor prognosis. In recent decades, intra-arterial administration of anti-cancer drugs has been considered a suitable alternative drug delivery route to intravenous and oral administration. Intra-arterial administration is believed to offer increasing drug responses by primary and metastatic brain tumors, and to be associated with better median overall survival. By directly injecting therapeutic agents into carotid or vertebral artery, intra-arterial administration rapidly increases intra-tumoral drug concentration but lowers systemic exposure. However, unexpected vascular or neural toxicity has questioned the therapeutic safety of intra-arterial drug administration and limits its widespread clinical application. Therefore, improving targeting and accuracy of intra-arterial administration has become a major research focus. This systematic review categorizes strategies for optimizing intra-arterial administration into five categories: (1) transient blood-brain barrier (BBB)/blood-tumor barrier (BTB) disruption, (2) regional cerebral hypoperfusion for peritumoral hemodynamic changes, (3) superselective endovascular intervention, (4) high-resolution imaging techniques, and (5) others such as cell and gene therapy. We summarize and discuss both preclinical and clinical research, focusing on advantages and disadvantages of different treatment strategies for a variety of cerebral tumor types.
依赖手术、放疗和全身化疗的脑肿瘤传统治疗方法往往伴随着高复发率和不良预后。近几十年来,动脉内给予抗癌药物被认为是一种优于静脉内和口服给药的合适的药物递送途径。动脉内给药被认为可增强原发性和转移性脑肿瘤对药物的反应,并与更好的中位总生存期相关。通过直接将治疗剂注入颈动脉或椎动脉,动脉内给药可迅速提高肿瘤内药物浓度,但降低全身暴露。然而,意外的血管或神经毒性对动脉内给药的治疗安全性提出了质疑,并限制了其广泛的临床应用。因此,提高动脉内给药的靶向性和准确性已成为主要研究重点。本系统综述将优化动脉内给药的策略分为五类:(1)短暂性血脑屏障(BBB)/血肿瘤屏障(BTB)破坏,(2)用于肿瘤周围血流动力学变化的局部脑灌注不足,(3)超选择性血管内介入,(4)高分辨率成像技术,以及(5)其他如细胞和基因治疗。我们总结并讨论了临床前和临床研究,重点关注针对各种脑肿瘤类型的不同治疗策略的优缺点。