Department of Interventional Radiology, the First Hospital of China Medical University, Shenyang 110001, China.
Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
Int J Med Sci. 2020 Aug 25;17(15):2269-2275. doi: 10.7150/ijms.46165. eCollection 2020.
Cancer vasculature is immature, disorganized and hyperpermeable and can serve as a target for anti-cancer therapies. Vascular disrupting agents (VDAs) are tubulin protein binding and depolymerizing agents that induce rapid tumoral vascular shutdown and subsequent cancer necrosis. However, two clinical problems exist with all VDAs, i.e. 1) incomplete anticancer effect and 2) dose-dependent toxicity. To tackle these problems, in our ongoing research, a novel VDA C118P is applied by transarterial administration of half the intravenous dose in rabbits with implanted VX2 liver tumor to assess its therapeutic efficacy. Nearly complete tumor necrosis was achieved by only a single arterial dose of C118P at 5 mg/kg, which was documented in a representative case by in vivo digital subtraction arteriogram (DSA) and magnetic resonance imaging (MRI), and further confirmed by ex vivo microangiogram and histopathology. This convincing and promising preliminary outcome would warrant further comprehensive studies to explore the potentials of VDAs by transarterial administration either in mono-drug or in combination for management of solid cancers.
肿瘤血管不成熟、紊乱且过度通透，可作为抗癌疗法的靶点。血管破坏剂（VDA）是微管蛋白结合和去聚合剂，可诱导肿瘤血管迅速关闭和随后的癌症坏死。然而，所有 VDA 都存在两个临床问题，即 1）抗癌效果不完全，2）剂量依赖性毒性。为了解决这些问题，在我们正在进行的研究中，通过向植入 VX2 肝肿瘤的兔子的动脉内给予半剂量的新型 VDA C118P，来评估其治疗效果。通过仅以 5mg/kg 的单次动脉剂量 C118P，即可实现近乎完全的肿瘤坏死，这在一个代表性病例中通过体内数字减影血管造影（DSA）和磁共振成像（MRI）得到了证实，并通过离体微血管造影和组织病理学进一步得到了确认。这一令人信服和有前途的初步结果将需要进一步进行全面研究，以探索通过动脉内给药的 VDA 单药或联合用于实体瘤治疗的潜力。
