Röth Alexander, Harley Calvin B, Baerlocher Gabriela M
Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122, Essen, Germany.
Recent Results Cancer Res. 2010;184:221-34. doi: 10.1007/978-3-642-01222-8_16.
Telomeres and telomerase play essential roles in the regulation of the lifespan of human cells. While normal human somatic cells do not or only transiently express telomerase and therefore shorten their telomeres with each cell division, most human cancer cells typically express high levels of telomerase and show unlimited cell proliferation. High telomerase expression allows cells to proliferate and expand long-term and therefore supports tumor growth. Owing to the high expression and its role, telomerase has become an attractive diagnostic and therapeutic cancer target. Imetelstat (GRN163L) is a potent and specific telomerase inhibitor and so far the only drug of its class in clinical trials. Here, we report on the structure and the mechanism of action of imetelstat as well as about the preclinical and clinical data and future prospects using imetelstat in cancer therapy.
端粒和端粒酶在调控人类细胞寿命方面发挥着重要作用。正常人类体细胞不表达或仅短暂表达端粒酶，因此随着每次细胞分裂端粒会缩短，而大多数人类癌细胞通常高表达端粒酶并表现出无限增殖能力。高端粒酶表达使细胞能够长期增殖和扩增，从而促进肿瘤生长。由于其高表达及其作用，端粒酶已成为一个有吸引力的癌症诊断和治疗靶点。艾美拉唑（GRN163L）是一种强效且特异性的端粒酶抑制剂，也是目前唯一进入临床试验阶段的该类药物。在此，我们报告艾美拉唑的结构、作用机制以及其在癌症治疗中的临床前和临床数据及未来前景。
