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Document Type |
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Article In Journal |
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Document Title |
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Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies |
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Document Language |
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English |
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Abstract |
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Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell
divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by
telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors.
Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in
mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human
telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of
telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the
activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop
telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed
key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA
synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize
telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to
reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its
function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of
telomerase inhibitors, as well as potential novel targets, will be summarized. |
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ISSN |
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1756-994X |
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Journal Name |
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Genome medicine |
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Volume |
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8 |
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Issue Number |
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1 |
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Publishing Year |
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1437 AH
2016 AD |
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Article Type |
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Article |
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Added Date |
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Tuesday, July 18, 2017 |
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Researchers
| Mohammad A Jafri | Jafri, Mohammad A | Researcher | Doctorate | |
| Shakeel A Ansari | Ansari, Shakeel A | Researcher | Doctorate | |
| Mohammed H Alqahtani | Alqahtani, Mohammed H | Researcher | Doctorate | |
| Jerry W Shay | Shay, Jerry W | Researcher | Doctorate | |
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