Siemann Dietmar W, Chaplin David J, Walicke Patricia A
Department of Radiation Oncology, University of Florida, 2000 SW Archer Road, Gainesville, FL 32610, USA.
Expert Opin Investig Drugs. 2009 Feb;18(2):189-97. doi: 10.1517/13543780802691068.
Vascular-disrupting strategies impair a tumor's blood vessel network, which is essential for tumor progression and metastasis. Vascular-disrupting agents (VDAs) cause a rapid and selective vascular shutdown in tumors to produce extensive secondary neoplastic cell death due to ischemia. A lead agent in this therapeutic strategy is the tubulin depolymerizing agent combretastatin-A4 phosphate (CA4P). Used alone, CA4P induces extensive necrosis in a wide variety of preclinical cancer models and significant blood flow reductions in the patient tumors. Preclinical and clinical data further indicate that CA4P can effectively be combined with chemotherapy or radiotherapy. Finally, the potential of combining VDAs with antiangiogenic therapies has shown considerable promise in preclinical models and such combinations are now beginning to be evaluated in patients.
血管破坏策略会损害肿瘤的血管网络，而血管网络对肿瘤进展和转移至关重要。血管破坏剂（VDA）会导致肿瘤内血管迅速且选择性地关闭，因缺血而产生广泛的继发性肿瘤细胞死亡。该治疗策略中的一种先导药物是微管解聚剂磷酸考布他汀-A4（CA4P）。单独使用时，CA4P在多种临床前癌症模型中可诱导广泛坏死，并使患者肿瘤中的血流量显著降低。临床前和临床数据进一步表明，CA4P可有效地与化疗或放疗联合使用。最后，在临床前模型中，将VDA与抗血管生成疗法联合使用的潜力已显示出相当大的前景，目前此类联合疗法已开始在患者中进行评估。
