Kudchadkar Ragini, Gonzalez Rene, Lewis Karl D
University of Colorado Cancer Center, Aurora, CO 80045, USA.
Expert Opin Investig Drugs. 2008 Nov;17(11):1769-76. doi: 10.1517/13543784.17.11.1769.
Growth factors that stimulate angiogenesis are vital in tumor development and maintenance. Inhibitors of angiogenesis are emerging as key elements in anticancer treatments, and now antibodies and small molecule kinase inhibitors are approved in the treatment of a variety of solid tumors. These have shown modest but statistically significant benefit in colon, breast and lung cancers. PI-88 has a novel mechanism of action compared to the drugs on the market today. By inhibiting heparanase, PI-88 blocks angiogenesis on several different cellular and biological levels. Promising results from Phase I/II trials are being seen with PI-88 in a variety of tumor types including melanoma and hepatocellular carcinoma. However, the development of antibody-induced thrombocytopenia has limited its use in some patients.
刺激血管生成的生长因子在肿瘤发展和维持过程中至关重要。血管生成抑制剂正成为抗癌治疗的关键要素，目前抗体和小分子激酶抑制剂已被批准用于治疗多种实体瘤。这些药物在结肠癌、乳腺癌和肺癌治疗中显示出适度但具有统计学意义的疗效。与目前市场上的药物相比，PI - 88具有全新的作用机制。通过抑制乙酰肝素酶，PI - 88在多个不同的细胞和生物学水平上阻断血管生成。PI - 88在包括黑色素瘤和肝细胞癌在内的多种肿瘤类型的I/II期试验中取得了令人鼓舞的结果。然而，抗体诱导的血小板减少症的出现限制了其在部分患者中的应用。
