BioDeakin, Institute for Technology & Research Innovation (ITRI), Geelong Technology Precinct (GTP), Deakin University, Pigdons Road, Waurn Ponds, Geelong, Victoria 3217, Australia.
Curr Med Chem. 2010;17(15):1509-15. doi: 10.2174/092986710790979935.
Apoptosis occurs via extrinsic or intrinsic signalling each triggered and regulated by many different molecular pathways. In recent years, the selective induction of apoptosis through survivin in tumour cells has been increasingly recognized as a promising approach for cancer therapy. Survivin has multiple functions including cytoprotection, inhibition of cell death, and cell-cycle regulation, especially at the mitotic process stage, all of which favour cancer survival. Many studies on clinical specimens have shown that survivin over expression is invariably up regulated in human cancers, associated with resistance to chemotherapy or radiation therapy, and linked to poor prognosis, suggesting that cancer cells survive with survivin. On the basis of these findings, survivin has been proposed as an attractive target for new anticancer interventions. Survivin inhibitors recently entered clinical trials. Recent studies suggest a possible role for survivin in regulating the function of normal adult cells. However, the expression and function of survivin in normal tissues are still not well characterized and understood. Still better understandings of survivin's role in tumour versus normal cells are needed for designing the strategies to selectively disrupt survivin in cancers. In the present review, we summarise the importance of recent survivin-targeted cancer therapy for future clinical application.
细胞凋亡可通过外在或内在信号通路触发和调节，这些信号通路由许多不同的分子途径触发和调节。近年来，通过survivin 选择性诱导肿瘤细胞凋亡已被越来越多地认为是癌症治疗的一种有前途的方法。Survivin 具有多种功能，包括细胞保护、抑制细胞死亡和细胞周期调控，特别是在有丝分裂过程阶段，这些都有利于癌症的存活。许多临床标本研究表明，survivin 在人类癌症中总是过度表达，与化疗或放疗耐药有关，并与预后不良相关，这表明癌细胞在 survivin 的作用下存活。基于这些发现，survivin 已被提议作为新抗癌干预的有吸引力的靶点。survivin 抑制剂最近已进入临床试验。最近的研究表明 survivin 可能在调节正常成年细胞的功能方面发挥作用。然而，survivin 在正常组织中的表达和功能仍未得到很好的描述和理解。为了设计在癌症中选择性破坏 survivin 的策略，需要更好地了解 survivin 在肿瘤细胞与正常细胞中的作用。在本综述中，我们总结了最近针对 survivin 的癌症治疗在未来临床应用中的重要性。
