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[摘要]：ASA404 (DMXAA, formerly AS1404) was originaly synthesized at the Auckland Cancer Society Research Centre in an effort to identfy more active analogues of flavone acetic acid (FAA). Phasse I trials of ASA404 were based on its curative properties in murine transplantable tumors at 15 fold increased potency over FAA Phase II studies showed acitvity for ASA404 in combination with standard chemotherapy is lung and prostate cancers, and phase III studies in lung cancers commenced in 2008. ASA404 exerts its antitumor effects party through inhibiton of tumor blood flow, but unlike other small-molecule vascular targeting agents under clinical investigation, it does not act through modulation of the tubulin cytoskeleton of vascular endothelial cells. While the molecular target of ASA404 is unknown, a hallmark of its preclinical activity is its induction of cytokine production within the tumor tissue. These cytokines confer a multiplicity of indirect effects, including vascular collapse and enhanced immune response, making ASA404 one of the most promising agents of its class under clinical developement. |
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