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传统抗癌疗法与端粒维持机制

Conventional anticancer therapeutics and telomere maintenance mechanisms.

作者信息

Uziel Orit, Lahav Meir

机构信息

Department of Medicine A, Rabin Medical Center, Beilinson Campus, Petah-Tikva, ISRAEL, 49100.

出版信息

Curr Pharm Des. 2014;20(41):6452-65. doi: 10.2174/1381612820666140630100130.

Abstract

The telomere-telomerase system has a unique role in the biology of cancer. Telomere maintenance, mostly affected by the up regulation of telomerase activity, is a prerequisite for perpetuation of malignant cells. This fundamental biologic feature defines telomere maintenance as an attractive therapeutic target for most types of cancer. This review summarizes some critical aspects of telomere biology with special emphasis on the connection to anticancer therapy. In particular, the effects on the telomere - telomerase system of conventional anticancer treatments, including various cytotoxic drugs, targeted biological agents and radiotherapy, and their possible combination with telomerase-directed therapy are discussed. Several potential problems, including side effects and complications inherent to perturbations of telomere biology in normal cells, are also highlighted. In spite of significant progress in this field, there are still several issues that have to be addressed and ultimately resolved in order to obtain a better characterization of the pros and cons of telomerase-directed therapies and, consequently, their clinical relevance.

摘要

端粒-端粒酶系统在癌症生物学中具有独特作用。端粒维持主要受端粒酶活性上调影响,是恶性细胞永存的先决条件。这一基本生物学特征将端粒维持定义为大多数类型癌症有吸引力的治疗靶点。本综述总结了端粒生物学的一些关键方面,特别强调了与抗癌治疗的联系。尤其讨论了包括各种细胞毒性药物、靶向生物制剂和放疗在内的传统抗癌治疗对端粒-端粒酶系统的影响,以及它们与端粒酶导向治疗联合的可能性。还强调了几个潜在问题,包括正常细胞中端粒生物学扰动所固有的副作用和并发症。尽管该领域取得了显著进展,但仍有几个问题必须加以解决并最终得到解决,以便更好地描述端粒酶导向治疗的利弊,从而确定其临床相关性。

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