The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications
Open Access
- 11 April 2020
- Vol. 12 (4), 949
- https://doi.org/10.3390/cancers12040949
Abstract
Telomere maintenance mechanisms (i.e., telomerase activity (TA) and the alternative lengthening of telomere (ALT) mechanism) contribute to tumorigenesis by providing unlimited proliferative capacity to cancer cells. Although the role of either telomere maintenance mechanisms seems to be equivalent in providing a limitless proliferative ability to tumor cells, the contribution of TA and ALT to the clinical outcome of patients may differ prominently. In addition, several strategies have been developed to interfere with TA in cancer, including Imetelstat that has been the first telomerase inhibitor tested in clinical trials. Conversely, the limited information available on the molecular underpinnings of ALT has hindered thus far the development of genuine ALT-targeting agents. Moreover, whether anti-telomerase therapies may be hampered or not by possible adaptive responses is still debatable. Nonetheless, it is plausible hypothesizing that treatment with telomerase inhibitors may exert selective pressure for the emergence of cancer cells that become resistant to treatment by activating the ALT mechanism. This notion, together with the evidence that both telomere maintenance mechanisms may coexist within the same tumor and may distinctly impinge on patients’ outcomes, suggests that ALT may exert an unexpected role in tumor biology that still needs to be fully elucidated.Funding Information
- Fondazione AIRC per la Ricerca sul Cancro (22933, 15194)
This publication has 61 references indexed in Scilit:
- A new role for histone deacetylase 5 in the maintenance of long telomeresThe FASEB Journal, 2013
- Alternative lengthening of telomeres in normal mammalian somatic cellsGenes & Development, 2013
- Telomere maintenance mechanisms in malignant peripheral nerve sheath tumors: expression and prognostic relevanceNeuro-Oncology, 2012
- Antitelomerase Therapy Provokes ALT and Mitochondrial Adaptive Mechanisms in CancerCell, 2012
- Alternative lengthening of telomeres in hTERT‐inhibited laryngeal cancer cellsCancer Science, 2010
- Assaying and investigating Alternative Lengthening of Telomeres activity in human cells and cancersFEBS Letters, 2010
- Alternative lengthening of telomeres: models, mechanisms and implicationsNature Reviews Genetics, 2010
- DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activityNature Biotechnology, 2009
- A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferasesNature Structural & Molecular Biology, 2008
- Telomeric Recombination in Mismatch Repair Deficient Human Colon Cancer Cells after Telomerase InhibitionCancer Research, 2004