Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin.
Impacting tumor cell-fate by targeting the inhibitor of apoptosis protein survivin.
复制标题
DOI：
10.1186/1476-4598-10-35
复制
发表时间：
2011-04-06
期刊：
影响因子：
37.3
通讯作者：
Morris JC
中科院分区：
文献类型：
--
作者：
Kelly RJ;Lopez-Chavez A;Citrin D;Janik JE;Morris JC
Survivin(BIRC5)是凋亡抑制蛋白(IAP)家族中的一员，它抑制caspase并阻止细胞死亡，在癌症中高表达，并与较差的临床预后有关。Survivin在细胞分裂和凋亡抑制过程中同时发挥作用，在决定细胞存活的过程中发挥着关键作用。通过分子图谱分析，Survivin一直被认为与更高的肿瘤分级、更晚期的疾病、更短的生存期、更快的复发率以及化疗和辐射耐受有关。Survivin在肿瘤组织中的不同于正常组织的表达，以及在许多细胞通路中作为节点蛋白的作用，使其成为高度灵活的治疗靶点，适合小分子抑制剂、分子拮抗剂和疫苗为基础的治疗。通过靶向Survivin，人们希望可以同时禁用多个肿瘤信号通路。这种效应可能适用于许多肿瘤组织，而不考虑特定的基因构成。到目前为止，Survivin抑制剂作为单一药物显示出适度的活性，但预计当与细胞毒化疗或单抗联合使用时，它们可能会显示出更强的疗效。这篇综述讨论了人类癌症中Survivin的复杂电路，并重点介绍了针对这一重要蛋白的新型药物的临床试验。
Survivin (BIRC5), a member of the inhibitor of apoptosis protein (IAP) family that inhibits caspases and blocks cell death is highly expressed in cancer and is associated with a poorer clinical outcome. Functioning simultaneously during cell division and apoptosis inhibition, survivin plays a pivotal role in determining cell survival. Survivin has consistently been identified by molecular profiling analysis to be associated with higher tumor grade, more advanced disease, abbreviated survival, accelerated rates of recurrence, and chemotherapy and radiation resistance. Survivin's differential expression in cancer compared to normal tissue and its role as a nodal protein in a number of cellular pathways make it a highly flexible therapeutic target, suitable for small-molecule inhibitiors, molecular antagonists, and vaccination-based therapies. By targeting survivin it is hoped that multiple tumor signaling circuitries may be simultaneously disabled. This effect may be applicable to many tumor histologies irrespective of specific genetic makeup. To date, survivin inhibitors have shown modest activity as single agents, but it is anticipated that when given in combination with cytotoxic chemotherapy or monoclonal antibodies they may exhibit enhanced efficacy. This review discusses the complex circuitry of survivin in human cancers and highlights clinical trials involving novel agents that target this important protein.
登录
查看更多内容
影响因子：
11.4
作者：
Ansell, SM;Arendt, BK;Fielding, A
通讯作者：
Fielding, A
影响因子：
20.3
作者：
Che, Xiao-Fang;Zheng, Chun-Lei;Akiyama, Shin-ichi
通讯作者：
Akiyama, Shin-ichi
影响因子：
7.5
作者：
Cohen, C;Lohmann, CM;Santoianni, R
通讯作者：
Santoianni, R
影响因子：
4.8
作者：
Dohi, T;Okada, K;Altieri, DC
通讯作者：
Altieri, DC
影响因子：
7.5
作者：
Altieri, Dario C.
通讯作者：
Altieri, Dario C.