Ryan Bríd M, O'Donovan Norma, Duffy Michael J
Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA.
Cancer Treat Rev. 2009 Nov;35(7):553-62. doi: 10.1016/j.ctrv.2009.05.003. Epub 2009 Jun 25.
Survivin is one of the most cancer-specific proteins identified to date, being upregulated in almost all human tumors. Biologically, survivin has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis. Because of its upregulation in malignancy and its key role in apoptosis, proliferation and angiogenesis, survivin is currently attracting considerable attention as a new target for anti-cancer therapies. In several animal model systems, downregulation of survivin or inactivation of its function has been shown to inhibit tumor growth. Strategies under investigation to target survivin include antisense oligonucleotides, siRNA, ribozymes, immunotherapy and small molecular weight molecules. The translation of these findings to the clinic is currently ongoing with a number of phase I/II clinical trials targeting survivin in progress. These include use of the antisense oligonucleotide LY2181308, the low molecular weight molecule inhibitor YM155 and survivin-directed autologous cytotoxic T lymphocytes. The optimum use of survivin antagonists in the treatment of cancer is likely to be in combination with conventional cancer therapies.
生存素是迄今为止发现的最具癌症特异性的蛋白质之一，在几乎所有人类肿瘤中均上调。从生物学角度来看，生存素已被证明可抑制细胞凋亡、增强增殖并促进血管生成。由于其在恶性肿瘤中的上调以及在细胞凋亡、增殖和血管生成中的关键作用，生存素目前作为抗癌治疗的新靶点备受关注。在多个动物模型系统中，生存素的下调或其功能的失活已被证明可抑制肿瘤生长。正在研究的靶向生存素的策略包括反义寡核苷酸、小干扰RNA（siRNA）、核酶、免疫疗法和小分子。目前正在将这些研究结果转化到临床，多项针对生存素的I/II期临床试验正在进行中。这些试验包括使用反义寡核苷酸LY2181308、低分子量分子抑制剂YM155以及针对生存素的自体细胞毒性T淋巴细胞。生存素拮抗剂在癌症治疗中的最佳应用可能是与传统癌症疗法联合使用。
