Targeting the telomere and shelterin complex for cancer therapy: current views and future perspectives.
Targeting the telomere and shelterin complex for cancer therapy: current views and future perspectives.
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DOI：
10.1111/j.1582-4934.2010.01253.x
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发表时间：
2011-02
影响因子：
5.3
通讯作者：
Keith WN
中科院分区：
文献类型：
--
作者：
Bilsland AE;Cairney CJ;Keith WN
异常的端粒稳态是细胞不朽所必需的，使细胞能够逃避端粒依赖性衰老。端粒酶抑制剂的详细临床前评估表明，端粒结构和功能在癌细胞中的破坏是高毒性的。在端粒酶抑制作用下，细胞必须分裂得足够频繁，以使一个或多个端粒缩短到不受保护的长度。功能端粒通过DNA重塑和端粒结合复合物庇护蛋白的其他活动来掩盖DNA损伤机制。对庇护蛋白的直接干扰已被证明会导致细胞死亡，而直接靶向端粒DNA的小分子也具有部分依赖于庇护蛋白破坏的抗肿瘤作用。然而，庇护素成分本身通常不被视为治疗靶点。在这篇综述中，我们探讨了庇护蛋白复合物治疗靶向的可能性。
Aberrant telomere homeostasis is essential for cell immortality, enabling cells to evade telomere dependent senescence. Disruption of telomere structure and function in cancer cells is highly toxic as shown by detailed pre-clinical evaluation of telomerase inhibitors. Under telomerase inhibition, cells must divide sufficiently frequently to allow one or more telomeres to shorten to an unprotected length. Functioning telomeres are disguised from the DNA damage machinery by DNA remodelling and other activities of the telomere binding complex shelterin. Direct interference with shelterin has been shown to result in cell killing and small molecules directly targeting telomere DNA also have anti-tumour effects partially dependent on shelterin disruption. However, shelterin components have not generally been regarded as therapeutic targets in their own right. In this review, we explore the possibilities for therapeutic targeting of the shelterin complex.
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影响因子：
8
作者：
Ni Chonghaile T;Letai A
通讯作者：
Letai A
影响因子：
8.4
作者：
Binz, N;Shalaby, T;Grotzer, MA
通讯作者：
Grotzer, MA
影响因子：
16.8
作者：
Amiard, Simon;Doudeau, Michel;Giraud-Panis, Marie-Josephe
通讯作者：
Giraud-Panis, Marie-Josephe
影响因子：
8
作者：
Gazdar, A. F.
通讯作者：
Gazdar, A. F.
影响因子：
8.4
作者：
Folini, M;Brambilla, C;Zaffaroni, N
通讯作者：
Zaffaroni, N