Functional and mechanistic analysis of telomerase: An antitumor drug target

详细信息    查看全文

• 作者：Yinnan Chen^b ; Yanmin Zhang^a ; ^{zhang2008@mail.xjtu.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：TERT ; Telomerase reverse transcriptase ; hTERT ; Human telomerase reverse transcriptase ; RT ; Reverse transcriptase ; TR ; Telomerase RNA ; hTR ; Human telomerase RNA ; RNP ; Ribonucleoprotein ; TEN ; Essential N-terminal domain ; TRBD ; Telomerase RNA binding domain ; CTE ; C-terminal extension domain ; CR4/5 ; Conserved region 4 and 5 ; TBE ; Template boundary element ; ROS ; Reactive oxygen specie ; G4 ; G-quadruplexes ; ALT ; Alternative lengthening of telomeres ; EGF ; Epidermal growth factor ; bFGF ; Basic fibroblast
• 刊名：Pharmacology and Therapeutics
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：163
• 期：Complete
• 页码：24-47
• 全文大小：1219 K

文摘

The current research on anticancer drugs focuses on exploiting particular traits or hallmarks unique to cancer cells. Telomerase, a special reverse transcriptase, has been recognized as a common factor in most tumor cells, and in turn a distinctive characteristic with respect to non-malignant cells. This feature has made telomerase a preferred target for anticancer drug development and cancer therapy. This review aims to analyze the pharmacological function and mechanism and role of telomerase in oncogenesis; to provide fundamental knowledge for research on the structure, function, and working mechanism of telomerase; to expound the role that telomerase plays in the initiation and development of tumor and its relationship with tumor cell growth, proliferation, apoptosis, and related pathway molecules; and to display potential targets of antitumor drug for inhibiting the expression, reconstitution, and trafficking of the enzyme. We therefore summarize recent advances in potential telomerase inhibitors for antitumor including natural products, synthetic small molecules, peptides and proteins, which indicate that optimizing the delivery method and drug combination could be of help in a combinatorial drug treatment for tumor. More extensive understanding of the structure, biogenesis, and mechanism of telomerase will provide invaluable information for increasing the efficiency of rational antitumor drug design.