Telomeres have been a subject of genetic research since the 1930s. They play a crucial role in cancer biology, as they influence both cellular senescence and genomic stability. In cancer cells, dysfunctional telomeres can lead to chromosomal fusions and, through deregulation of telomerase, allow replication of mutated chromosomes that might otherwise lead to apoptosis. Research is now focused on improving telomere-based cancer cell detection and developing potential therapies that inhibit telomerase activity in cancerous cells. Telomere research is crucial in understanding the molecular mechanisms influencing tumor growth and invasiveness because of the central role played by telomeres in various cancer types. Several telomerase inhibitors and immunotherapy treatments are in pre-clinical or clinical development. Research on the role of telomeres in oncogenesis has made significant strides, but obstacles remain, including a lack of high-resolution structural understanding, inadequate preclinical models, and concern over potential side effects. Even so, the current path of telomere research holds promise.
Britannica, T. and Editors of Encyclopaedia (2024) Hermann Joseph Muller. Encyclopedia Britannica. https://www.britannica.com/biography/Hermann-Joseph-Muller
Cold Spring Harbor Laboratory (2021) Barbara McClintock Cold Spring Harbor Laboratory. https://www.cshl.edu/personal-collections/barbara-mcclintock/
Zakian, V.A. (2012) Telomeres: The Beginnings and Ends of Eukaryotic Chromosomes. Experimental Cell Research , 318, 1456-1460. https://doi.org/10.1016/j.yexcr.2012.02.015
Chakravarti, D., LaBella, K.A. and DePinho, R.A. (2021) Telomeres: History, Health, and Hallmarks of Aging. Cell , 184, 306-322. https://doi.org/10.1016/j.cell.2020.12.028
Corey, D.R. (2009) Telomeres and Telomerase: From Discovery to Clinical Trials. Chemistry & Biology , 16, 1219-1223. https://doi.org/10.1016/j.chembiol.2009.12.001
Cong, Y., Wright, W.E. and Shay, J.W. (2002) Human Telomerase and Its Regulation. Microbiology and Molecular Biology Reviews , 66, 407-425. https://doi.org/10.1128/mmbr.66.3.407-425.2002
Timashev, L.A. and de Lange, T. (2020) Characterization of T-Loop Formation by TRF2. Nucleus , 11, 164-177. https://doi.org/10.1080/19491034.2020.1783782
Maciejowski, J. and de Lange, T. (2017) Telomeres in Cancer: Tumour Suppression and Genome Instability. Nature Reviews Molecular Cell Biology , 18, 175-186. https://doi.org/10.1038/nrm.2016.171
Reddel, R. (2014) Telomere Maintenance Mechanisms in Cancer: Clinical Implications. Current Pharmaceutical Design , 20, 6361-6374. https://doi.org/10.2174/1381612820666140630101047
Tsatsakis, A., Oikonomopoulou, T., Nikolouzakis, T., Vakonaki, E., Tzatzarakis, M., Flamourakis, M., et al . (2023) Role of Telomere Length in Human Carcinogenesis (Review). International Journal of Oncology , 63, Article No. 78. https://doi.org/10.3892/ijo.2023.5526
Recagni, M., Bidzinska, J., Zaffaroni, N. and Folini, M. (2020) The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications. Cancers , 12, Article 949. https://doi.org/10.3390/cancers12040949
Tham, C., Poon, L., Yan, T., Koh, J.Y.P., Ramlee, M.K., Teoh, V.S.I., et al . (2023) High-Throughput Telomere Length Measurement at Nucleotide Resolution Using the Pacbio High Fidelity Sequencing Platform. Nature Communications , 14, Article No. 281. https://doi.org/10.1038/s41467-023-35823-7
Montpetit, A.J., Alhareeri, A.A., Montpetit, M., Starkweather, A.R., Elmore, L.W., Filler, K., et al . (2014) Telomere Length. Nursing Research , 63, 289-299. https://doi.org/10.1097/nnr.0000000000000037
Fernandez-Garcia, I., Ortiz-de-Solorzano, C. and Montuenga, L.M. (2008) Telomeres and Telomerase in Lung Cancer. Journal of Thoracic Oncology , 3, 1085-1088. https://doi.org/10.1097/jto.0b013e3181886713
George, S.L., Parmar, V., Lorenzi, F., Marshall, L.V., Jamin, Y., Poon, E., et al . (2020) Novel Therapeutic Strategies Targeting Telomere Maintenance Mechanisms in High-Risk Neuroblastoma. Journal of Experimental & Clinical Cancer Research , 39, Article No. 78. https://doi.org/10.1186/s13046-020-01582-2
Flynn, R.L., Cox, K.E., Jeitany, M., Wakimoto, H., Bryll, A.R., Ganem, N.J., et al . (2015) Alternative Lengthening of Telomeres Renders Cancer Cells Hypersensitive to ATR Inhibitors. Science , 347, 273-277. https://doi.org/10.1126/science.1257216
Flynn, R.L., Centore, R.C., O’Sullivan, R.J., Rai, R., Tse, A., Songyang, Z., et al . (2011) TERRA and hnRNPA1 Orchestrate an RPA-to-POT1 Switch on Telomeric Single-Stranded DNA. Nature , 471, 532-536. https://doi.org/10.1038/nature09772
Massachusetts General Hospital (20150 Inhibition of the Alternative Lengthening of Telomeres (ALT) Pathway. https://www.massgeneral.org/cancer-center/clinician-resources/advances/inhibition-of-the-alternative-lengthening-of-telomeres-alt-pathway
Medline Plus (2020) Heart Attack. https://medlineplus.gov/heartattack.html
Guterres, A.N. and Villanueva, J. (2020) Targeting Telomerase for Cancer Therapy. Oncogene , 39, 5811-5824. https://doi.org/10.1038/s41388-020-01405-w
Aviv, A., Anderson, J.J. and Shay, J.W. (2017) Mutations, Cancer and the Telomere Length Paradox. Trends in Cancer , 3, 253-258. https://doi.org/10.1016/j.trecan.2017.02.005
American Cancer Society (2019) Cancer Facts & Figures 2019. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf
Bailar, J.C. and Smith, E.M. (1986) Progress against Cancer? New England Journal of Medicine , 314, 1226-1232. https://doi.org/10.1056/nejm198605083141905
Darrow, J.J. (2022) Two Views of Cancer Medicines: Imagery versus Evidence. Health Marketing Quarterly , 40, 141-152. https://doi.org/10.1080/07359683.2021.1997512
Song, T., Li, H., Xu, W., Yu, Y., Xin, X. and Hui, D. (2006) Effect of 3'-Azido-3'-Deoxythymidine (AZT) on Telomerase Activity and Proliferation of HO-8910 Cell Line of Ovarian Cancer. International Journal of Biomedical Science , 2, 35-41. https://doi.org/10.59566/ijbs.2006.2035
Herbert, B., Wright, W.E. and Shay, J.W. (2001) Telomerase and Breast Cancer. Breast Cancer Research , 3, Article No. 146. https://doi.org/10.1186/bcr288
Lantuéjoul, S., Salon, C., Soria, J. and Brambilla, E. (2007) Telomerase Expression in Lung Preneoplasia and Neoplasia. International Journal of Cancer , 120, 1835-1841. https://doi.org/10.1002/ijc.22473
Blanco, D., Vicent, S., Fraga, M.F., Fernandez-Garcia, I., Freire, J., Lujambio, A., et al . (2007) Molecular Analysis of a Multistep Lung Cancer Model Induced by Chronic Inflammation Reveals Epigenetic Regulation of P16, Activation of the DNA Damage Response Pathway. Neoplasia , 9, 840-852. https://doi.org/10.1593/neo.07517
Röth, A., Harley, C.B. and Baerlocher, G.M. (2009) Imetelstat (GRN163L)—Telomerase-Based Cancer Therapy. In: Recent Results in Cancer Research , Springer, 221-234. https://doi.org/10.1007/978-3-642-01222-8_16
Zhu, S., Yang, M., Wang, T. and Ding, Z. (2023) Causal Relationships between Telomere Length and Liver Disease: A Mendelian Randomization Study. Frontiers in Genetics , 14, Article 1164024. https://doi.org/10.3389/fgene.2023.1164024
der Stroth, L., Tharehalli, U., Günes, C. and Lechel, A. (2020) Telomeres and Telomerase in the Development of Liver Cancer. Cancers , 12, Article 2048. https://doi.org/10.3390/cancers12082048