Functional and mechanistic analysis of telomerase: An antitumor drug target.
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.
School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, USA.
Yinnan
Y
Chen
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province 710061, PR China. Electronic address: zhang2008@mail.xjtu.edu.cn.
Yanmin
Y
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D049108:Cell Enlargement; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D015536:Down-Regulation; D016503:Drug Delivery Systems; D015195:Drug Design; D020035:Holoenzymes; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D028321:Plant Preparations / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D000089804:Shelterin Complex; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000378:metabolism*; D034501:Telomere-Binding Proteins / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation
D000970:Antineoplastic Agents; D015415:Biomarkers; D020035:Holoenzymes; D028321:Plant Preparations; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D019098:Telomerase
Drug target; Function; Mechanism; Telomerase; Tumor inhibitors