Skordalakes Emmanuel
Gene Expression & Regulation Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Future Oncol. 2009 Mar;5(2):163-7. doi: 10.2217/14796694.5.2.163.
Inappropriate activation of a single enzyme, telomerase, is associated with the uncontrollable proliferation of cells observed in as many as 90% of all of human cancers. Since the mid-1990s, when telomerase activity was detected in human tumors, scientists have eyed the enzyme as an ideal target for developing broadly effective anticancer drugs. One of the missing links in the effort to identify such therapies has been the high-resolution structure of the enzyme, a powerful tool used for the identification and development of clinical drugs. A recent structure of the catalytic subunit of teleomerase from the Skordalakes laboratory, a major advancement in the field of telomeres, has opened the door to the development of new, broadly effective cancer drugs, as well as anti-aging therapies. Here we present a brief description of telomerase biology, current efforts to identify telomerase function modulators and the potential importance of the telomerase structure in future drug development.
单一酶——端粒酶的不适当激活,与在多达90%的人类癌症中所观察到的细胞失控增殖相关。自20世纪90年代中期在人类肿瘤中检测到端粒酶活性以来,科学家们一直将该酶视为开发具有广泛疗效的抗癌药物的理想靶点。在寻找此类疗法的过程中,一个缺失的环节是该酶的高分辨率结构,这是用于临床药物鉴定和开发的强大工具。斯科尔达莱克斯实验室最近解析的端粒酶催化亚基结构,是端粒领域的一项重大进展,为开发新的、具有广泛疗效的癌症药物以及抗衰老疗法打开了大门。在此,我们简要介绍端粒酶生物学、目前鉴定端粒酶功能调节剂的工作,以及端粒酶结构在未来药物开发中的潜在重要性。