Telomerase inhibitors as anticancer therapy.
Telomerase inhibitors as anticancer therapy.
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端粒酶抑制剂作为抗癌疗法。
DOI：
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发表时间：
2002
期刊：
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通讯作者：
K. Anderson
中科院分区：
文献类型：
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作者：
M. Akiyama;T. Hideshima;N. Munshi;K. Anderson
端粒酶抑制剂被认为是一种新的癌症特异性治疗方法，因为大多数肿瘤细胞都有高水平的端粒酶表达，而大多数正常体细胞表达的端粒酶水平很低或检测不到。肿瘤细胞的持续增殖需要端粒酶的激活来维持染色体的稳定和延长寿命，因为端粒酶延长了端粒的长度并逆转了细胞有丝分裂的时钟。相反，通过抑制端粒酶活性而缩短端粒会导致肿瘤细胞的生长停滞(衰老)和凋亡。此外，已有研究表明，抑制端粒酶活性会增加肿瘤细胞对抗癌药物诱导的细胞凋亡的敏感性。因此，端粒酶抑制剂可以作为常规治疗的佐剂。然而，端粒酶抑制作为一种治疗策略也有几个潜在的局限性。例如，端粒酶抑制和端粒缩短之间存在滞后期，伴随着生长停滞和细胞死亡。在这篇综述中，我们将讨论端粒和端粒酶的基本生物学，作为开发基于端粒酶活性抑制的治疗方法的平台。
Telomerase inhibitors have been touted as a novel cancer specific therapy, as most tumor cells have high expression of telomerase, whereas most normal somatic cells express low or undetectable levels of telomerase. Continued proliferation of tumor cells requires activation of telomerase to maintain chromosomal stability and extend life span, because telomerase elongates telomere length and rewinds the cellular mitotic clock. Conversely, shortening of telomeres by inhibition of telomerase activity induces growth arrest (senescence) and apoptosis in tumor cells. Moreover, it has been reported that inhibition of telomerase increases the susceptibility of tumor cells to apoptosis induced by anticancer agents. Thus, telomerase inhibitors could be used as an adjuvant with conventional therapy. However, there are also several potential limitations of telomerase inhibition as a therapeutic strategy. For example, there is a lag phase between telomerase inhibition and telomere shortening, with growth arrest and cell death. In this review, we will discuss the basic biology of telomeres and telomerase as a platform for the development of treatments based upon inhibition of telomerase activity.