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- Publisher Website: 10.1002/mc.23035
- Scopus: eid_2-s2.0-85070885240
- PMID: 31062416
- WOS: WOS:000480583800004
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Article: In perspective: An update on telomere targeting in cancer
Title | In perspective: An update on telomere targeting in cancer |
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Authors | |
Keywords | 6-thio-dG ALT BRAF hTERC hTERT melanoma telomerase |
Issue Date | 2019 |
Citation | Molecular Carcinogenesis, 2019, v. 58, n. 9, p. 1581-1588 How to Cite? |
Abstract | Engaging a telomere maintenance mechanism during DNA replication is essential for almost all advanced cancers. The conversion from normal and premalignant somatic cells to advanced malignant cells often results (85%-90%) from the reactivation of the functional ribonucleoprotein holoenzyme complex, referred to as telomerase. Modulation of the human telomerase reverse transcriptase (hTERT) appears to be rate limiting to produce functional telomerase and engage a telomere maintenance mechanism. The remaining 10% to 15% of cancers overcome progressively shortened telomeres by activating an alternative lengthening of telomeres (ALT) maintenance mechanism, through a DNA recombination pathway. Exploration into the specific mechanisms of telomere maintenance in cancer have led to the development of drugs such as Imetelstat (GRN163L), BIBR1532, 6-thio-dG, VE-822, and NVP-BEZ235 being investigated as therapeutic approaches for treating telomerase and ALT tumors. The successful use of 6-thio-dG (a nucleoside preferentially recognized by telomerase) that targets and uncaps telomeres in telomerase positive but not normal telomerase silent cells has recently shown impressive effects on multiple types of cancer. For example, 6-thio-dG overcomes therapy-resistant cancers in a fast-acting mechanism potentially providing an alternative or additional route of treatment for patients with cancer. In this perspective, we provide a synopsis of the current landscape of telomeres and telomerase processing in cancer development and how this new knowledge may improve outcomes for patients with cancer. |
Persistent Identifier | http://hdl.handle.net/10722/318785 |
ISSN | 2021 Impact Factor: 5.139 2020 SCImago Journal Rankings: 1.254 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Sugarman, Eric T. | - |
dc.contributor.author | Zhang, Gao | - |
dc.contributor.author | Shay, Jerry W. | - |
dc.date.accessioned | 2022-10-11T12:24:33Z | - |
dc.date.available | 2022-10-11T12:24:33Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Molecular Carcinogenesis, 2019, v. 58, n. 9, p. 1581-1588 | - |
dc.identifier.issn | 0899-1987 | - |
dc.identifier.uri | http://hdl.handle.net/10722/318785 | - |
dc.description.abstract | Engaging a telomere maintenance mechanism during DNA replication is essential for almost all advanced cancers. The conversion from normal and premalignant somatic cells to advanced malignant cells often results (85%-90%) from the reactivation of the functional ribonucleoprotein holoenzyme complex, referred to as telomerase. Modulation of the human telomerase reverse transcriptase (hTERT) appears to be rate limiting to produce functional telomerase and engage a telomere maintenance mechanism. The remaining 10% to 15% of cancers overcome progressively shortened telomeres by activating an alternative lengthening of telomeres (ALT) maintenance mechanism, through a DNA recombination pathway. Exploration into the specific mechanisms of telomere maintenance in cancer have led to the development of drugs such as Imetelstat (GRN163L), BIBR1532, 6-thio-dG, VE-822, and NVP-BEZ235 being investigated as therapeutic approaches for treating telomerase and ALT tumors. The successful use of 6-thio-dG (a nucleoside preferentially recognized by telomerase) that targets and uncaps telomeres in telomerase positive but not normal telomerase silent cells has recently shown impressive effects on multiple types of cancer. For example, 6-thio-dG overcomes therapy-resistant cancers in a fast-acting mechanism potentially providing an alternative or additional route of treatment for patients with cancer. In this perspective, we provide a synopsis of the current landscape of telomeres and telomerase processing in cancer development and how this new knowledge may improve outcomes for patients with cancer. | - |
dc.language | eng | - |
dc.relation.ispartof | Molecular Carcinogenesis | - |
dc.subject | 6-thio-dG | - |
dc.subject | ALT | - |
dc.subject | BRAF | - |
dc.subject | hTERC | - |
dc.subject | hTERT | - |
dc.subject | melanoma | - |
dc.subject | telomerase | - |
dc.title | In perspective: An update on telomere targeting in cancer | - |
dc.type | Article | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1002/mc.23035 | - |
dc.identifier.pmid | 31062416 | - |
dc.identifier.scopus | eid_2-s2.0-85070885240 | - |
dc.identifier.volume | 58 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | 1581 | - |
dc.identifier.epage | 1588 | - |
dc.identifier.eissn | 1098-2744 | - |
dc.identifier.isi | WOS:000480583800004 | - |