文章：

验证生存素（Survivin）作为癌症治疗靶点

Validating survivin as a cancer therapeutic target

原文发布日期：2003-01-01

DOI: 10.1038/nrc968

类型: Review Article

开放获取: 否

要点：

1. In mammalian cells, apoptosis is modulated by two protein families — the BCL2 and inhibitor of apoptosis (IAP) families.
2. Survivin is a unique member of the IAP family. It is associated with several subcellular compartments and its expression is regulated by many signalling pathways.
3. The survivin pathway interfaces with both the cell-death machinery and mechanisms of cell-cycle progression and microtubule stability.
4. Survivin expression is undetectable in most normal adult tissues, but is overexpressed in virtually every human tumour that has been studied. Several mechanisms have been proposed to account for this overexpression, one of which is loss of wild-type p53.
5. Is survivin a rational target for cancer therapy? Using molecular antagonists of survivin is one approach for enhancing cell death — specifically of tumours — and could be used in combination with conventional chemotherapy- or radiation-based treatments.

要点翻译：

1. 在哺乳动物细胞中，凋亡过程受到两个蛋白质家族的调控——BCL2家族和凋亡抑制蛋白（IAP）家族。
2. 生存素（Survivin）是IAP家族的特殊成员，它存在于多个亚细胞区室中，其表达受多种信号通路调控。
3. 该通路既与细胞死亡机制相互作用，也参与细胞周期进程和微管稳定性的调节。
4. 在大多数正常成人组织中检测不到生存素的表达，但在几乎所有研究过的人类肿瘤中均存在过度表达。这种过度表达可能由多种机制引起，其中野生型p53基因的缺失是潜在原因之一。
5. 生存素是否能成为癌症治疗的合理靶点？使用生存素分子拮抗剂是增强细胞死亡（特别是肿瘤细胞）的一种策略，该方法可与传统化疗或放射治疗联合应用。

英文摘要：

Acquisition of the ability to evade cellular suicide, or apoptosis, is one of the master switches that contributes to cellular transformation and, ultimately, to invasive cancer. Much has been learned about the molecular organization of apoptotic pathways and their regulators, but the identification and validation of translational targets for apoptosis-based cancer therapy has posed a great challenge. Survivin is an attractive candidate for cancer therapy, so what is its potential applicability in the clinic?

摘要翻译： 

胰腺导管腺癌是一种侵袭性强、破坏力大的疾病，其特征是侵袭性、快速进展和对治疗的深度抵抗。病理分类和癌症遗传学的进展提高了我们对该疾病的描述性理解；然而，胰腺癌生物学的重要方面仍知之甚少。特定基因突变的致病作用是什么？起源细胞是什么？基质如何促进肿瘤发生？对胰腺癌生物学的更好理解应为更有效的治疗开辟道路。

原文链接：

Validating survivin as a cancer therapeutic target