Vascular disrupting agents (VDAs), a group of cancer remedies, can cause a specific and irreversible destruction of established tumor vessels, and the complete halt of blood flow in the tumor. DMXAA (ASA404) or Vadimezan, a flavone‐acetic acid‐based drug, is the most promising VDAs that induces a rapid shutdown of blood flow in tumors but not in normal tissue. The exact mechanism of vascular disruption is unknown; however, proposed direct and indirect mechanisms of action for DMXAA comprises (i) inducing apoptosis in endothelial cells; (ii) hemorrhagic necrosis and ischemia in tumor; (iii) release of serotonin (5‐HT); (vi) stimulation of innate immune system; (v) production of inflammatory cytokines, for example TNF, IL‐6, GCSF, KC, IP‐10, and MCP‐1; (vi) activation of NFκB and p38 (MAPK); (vii) production of nitric oxide; and (viii) reducing tumor energetics and membrane turnover. Despite the remarkable results from preclinical and phase I/II, DMXAA has failed in phase III clinical trials. The reason for this surprising discrepancy, among others, was discovered to be STING receptor variations between mice and humans. In this review, the development, the mechanisms of DMXAA action, the clinical trials, the combination therapy, and the future of this drug will be discussed.

中文翻译：

---

Vadimezan（DMXAA）概述：血管破坏剂

血管分裂剂（VDA）是一组癌症治疗药物，可导致已建立的肿瘤血管发生特定且不可逆转的破坏，并使肿瘤中的血流完全停止。DMXAA（ASA404）或以黄酮乙酸为基础的药物Vadimezan是最有前途的VDA，可诱导肿瘤中而非正常组织中的血流迅速关闭。血管破裂的确切机制尚不清楚；然而，提出的针对DMXAA的直接和间接作用机制包括：（i）诱导内皮细胞凋亡。（ii）肿瘤中的出血性坏死和局部缺血；（iii）释放5-羟色胺（5-HT）；（vi）刺激先天免疫系统；（v）产生炎性细胞因子，例如TNF，IL-6，GCSF，KC，IP-10和MCP-1；（vi）激活NFκB和p38（MAPK）；（vii）生产一氧化氮；（viii）减少肿瘤能量和膜更新。尽管临床前和I / II期取得了令人瞩目的成果，但DMXAA在III期临床试验中还是失败了。除其他外，发现这种令人惊讶的差异的原因是小鼠和人类之间的STING受体变异。在这篇综述中，将讨论DMXAA的发展，作用机理，临床试验，联合治疗以及该药物的未来。