Telomere Maintenance Mechanisms in Cancer: Clinical Implications

被引:64
|
作者
Reddel, Roger R. [1 ,2 ]
机构
[1] Childrens Med Res Inst, Westmead, NSW 2145, Australia
[2] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia
基金
英国医学研究理事会;
关键词
Alternative lengthening of telomeres; cancer; diagnosis; prognosis; telomerase; telomeres; therapy; TERT PROMOTER MUTATIONS; IMMORTAL HUMAN-CELLS; PROMYELOCYTIC LEUKEMIA BODIES; DNA-DAMAGE RESPONSE; HUMAN BREAST-CANCER; REVERSE-TRANSCRIPTASE; G-QUADRUPLEX; CLINICOPATHOLOGICAL PARAMETERS; HOMOLOGOUS RECOMBINATION; ALTERNATIVE MECHANISM;
D O I
10.2174/1381612820666140630101047
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The presence of immortal cell populations with an up-regulated telomere maintenance mechanism (TMM) is an almost universal characteristic of cancers, whereas normal somatic cells are unable to prevent proliferation-associated telomere shortening and have a limited proliferative potential. TMMs and related aspects of telomere structure and function therefore appear to be ideal targets for the development of anticancer therapeutics. Such treatments would be targeted to a specific cancer-related molecular abnormality, and also be broad-spectrum in that they would be expected to be potentially applicable to most cancers. However, the telomere biology of normal and malignant human cells is a relatively young research field with large numbers of unanswered questions, so the optimal design of TMM-targeted therapeutic approaches remains unclear. This review outlines the opportunities and challenges presented by telomeres and TMMs for clinical management of cancer.
引用
收藏
页码:6361 / 6374
页数:14
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