Is telomerase a viable target in cancer?

Buseman, Christen M.; Wright, Woodring E.; Shay, Jerry W.

doi:10.1016/j.mrfmmm.2011.07.006

Cited by 125 publications

(100 citation statements)

References 123 publications

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“…In the latter strategy, antisense oligonucleotides, small interfering RNAs and ribozymes can be applied for inhibition of TERT activity. GRN163L (also known as imetelstat) is the most studied antisense oligonucleotide that causes TERT inhibition and telomere shortening in cancer cell lines derived from different organs [13]. This compound leads to apoptosis of cells and to inhibition of tumour growth, and it is being used in clinical trials of several cancer types [13].…”

Section: Telomerase As a Therapeutic Targetmentioning

confidence: 99%

“…GRN163L (also known as imetelstat) is the most studied antisense oligonucleotide that causes TERT inhibition and telomere shortening in cancer cell lines derived from different organs [13]. This compound leads to apoptosis of cells and to inhibition of tumour growth, and it is being used in clinical trials of several cancer types [13]. DNA vaccines (immunotherapy) have been used to generate protective immunity against tumours in several models [96].…”

Section: Telomerase As a Therapeutic Targetmentioning

confidence: 99%

“…In vitro and in vivo studies showed tumour regression using TERT-based vaccination approaches (reviewed in [72]). Different peptides have been used to induce anti-TERT immune response [13] and vaccination using the I540-548 peptide showed anti-tumour responses in cancer [122]. Several preclinical studies using TERT peptides are being conducted (reviewed in [103]).…”

Section: Telomerase As a Therapeutic Targetmentioning

confidence: 99%

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Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and nonneoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

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Section: Telomerase As a Therapeutic Targetmentioning

confidence: 99%

Section: Telomerase As a Therapeutic Targetmentioning

confidence: 99%

Section: Telomerase As a Therapeutic Targetmentioning

confidence: 99%

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Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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“…(12)(13)(14)(15) Conversely, telomerase upregulation leads to the cellular immortalization that is fundamental to cancer cell growth. (16) Telomerase reverse transcriptase (TERT) known to has an essential role in telomere maintenance and in cancer biology. (17) The majority cancer cells depend on the activation of telomerase to gain proliferative immortality.…”

Section: Introductionmentioning

confidence: 99%

Telomere in Aging and Age-Related Diseases

2017

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B ACKGROUND:The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span. CONTENT:Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic Abstract R E V I E W A R T I C L Einstability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases' pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications. SUMMARY:Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management.

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“…Telomerase activity is not evident in normal cells, with elimination of germ cells and regeneration tissues (Buseman et al, 2012). Though, it is reactive currently in almost 80-90% of human cancer.…”

Section: Introductionmentioning

confidence: 99%

Diosgenin Inhibits hTERT Gene Expression in the A549 Lung Cancer Cell Line

Mohammad

Ghareghomi²,

Haddadchi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Diosgenin, a steroidal saponin from a therapeutic herb, fenugreek (Trigonellafoenum-graceum L.), has been recognized to have anticancer properties. Telomerase activity is not detected in typical healthy cells, while in cancer cell telomerase expression is reactivated, therefore providing a promising cancer therapeutic target. Materials and Methods: We studied the inhibitory effect of diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT-assays and qRT-PCR analysis were conducted to assess cytotoxicity and hTERT gene expression inhibition effects, respectively. Results: MTT results showed that IC 50 values for 24, 48 and 72h after treatment were 47, 44 and 43µM, respectively. Culturing cells with diosgenin treatment caused down-regulation of hTERT expression. Discussion: These results show that diosgenin inhibits telomerase activity by down-regulation of hTERT gene expression in the A549 lung cancer cell line

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Is telomerase a viable target in cancer?

Cited by 125 publications

References 123 publications

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

Telomere in Aging and Age-Related Diseases

Diosgenin Inhibits hTERT Gene Expression in the A549 Lung Cancer Cell Line

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