Georg Speyer Haus, Institute for Biomedical Research, Paul Ehrlich Str. 42, 60322, Frankfurt am Main, Germany,
BioDrugs. 2014 Feb;28(1):27-39. doi: 10.1007/s40259-013-0058-x.
Survivin is a well-established target in experimental cancer therapy. The molecule is over-expressed in most human tumors, but hardly detectable in normal tissues. Multiple functions in different subcellular compartments have been assigned. It participates in the control of cell division, apoptosis, the cellular stress response, and also in the regulation of cell migration and metastasis. Survivin expression has been recognized as a biomarker: high expression indicates an unfavorable prognosis and resistance to chemotherapeutic agents and radiation treatment. Survivin is an unconventional drug target and several indirect approaches have been exploited to affect its function and the phenotype of survivin-expressing cells. Interference with the expression of the survivin gene, the utilization of its messenger RNA, the intracellular localization, the interaction with binding partners, the stability of the survivin protein, and the induction of survivin-specific immune responses have been taken into consideration. A direct strategy to inhibit survivin has been based on the identification of a specifically interacting peptide. This peptide can recognize survivin intracellularly and cause the degradation of the ligand-survivin complex. Technology is being developed that might allow the derivation of small molecular-weight, drug-like compounds that are functionally equivalent to the peptide ligand.
Survivin 是实验性癌症治疗中一个成熟的靶点。该分子在大多数人类肿瘤中过度表达，但在正常组织中几乎检测不到。已经分配了其在不同亚细胞隔室中的多种功能。它参与细胞分裂、细胞凋亡、细胞应激反应的控制，也参与细胞迁移和转移的调节。Survivin 的表达已被认为是一种生物标志物：高表达表明预后不良，对化疗药物和放射治疗有耐药性。Survivin 是一个非传统的药物靶点，已经开发了几种间接方法来影响其功能和表达 survivin 的细胞表型。干扰 survivin 基因的表达、利用其信使 RNA、细胞内定位、与结合伴侣的相互作用、survivin 蛋白的稳定性以及诱导 survivin 特异性免疫反应都被考虑在内。抑制 survivin 的直接策略是基于鉴定一个特异性相互作用的肽。该肽可以在细胞内识别 survivin，并导致配体-survivin 复合物的降解。正在开发的技术可能允许衍生出与肽配体功能等效的小分子、类似药物的化合物。
