Telomere Length and Cancer

Authors

DOI:

https://doi.org/10.54133/ajms.v8i1.1615

Keywords:

Cancer, Shelterin, Telomeres, Telomere shortening

Abstract

Telomeres, the protective caps at the ends of human chromosomes, shorten with each round of cell division, representing a counter in the form of a biological clock. Beyond 50 to 60 divisions, the protective function of the telomeres will become unsustainable, and cells will usually experience senescence and death. Loss of cell function is manifested in the form of aging and the onset of diseases, including cancer. Cancer cells have found a way around this by overexpressing an enzyme, called telomerase, which counteracts the telomere shortening, thus allowing the neoplastic cells to keep replicating. This narrative review outlines why telomeres undergo shortening and how cancer cells exploit and take advantage of that phenomenon. The fact that malignant cells derail the biological telomere clock could be targeted for therapeutic benefit. The review also highlights the diverse telomere-based strategies explored in cancer treatment.

Downloads

Download data is not yet available.

References

Nassour J, Schmidt TT, Karlseder J. Telomeres and cancer: Resolving the paradox. Annu Rev Cancer Biol. 2021;5(1):59-77. doi: 10.1146/annurev-cancerbio-050420-023410. DOI: https://doi.org/10.1146/annurev-cancerbio-050420-023410

Pfeiffer V, Lingner J. Replication of telomeres and the regulation of telomerase. Cold Spring Harb Perspect Biol. 2013;5(5):a010405. doi: 10.1101/cshperspect.a010405. DOI: https://doi.org/10.1101/cshperspect.a010405

Webb CJ, Wu Y, Zakian VA. DNA repair at telomeres: keeping the ends intact. Cold Spring Harb Perspect Biol. 2013;5(6):a012666. doi: 10.1101/cshperspect.a012666. DOI: https://doi.org/10.1101/cshperspect.a012666

Heidenreich B, Kumar R. TERT promoter mutations in telomere biology. Mutat Res Rev Mutat Res. 2017;771:15-31. doi: 10.1016/j.mrrev.2016.11.002. DOI: https://doi.org/10.1016/j.mrrev.2016.11.002

Collins K. Single-stranded DNA repeat synthesis by telomerase. Curr Opin Chem Biol. 2011;15(5):643-648. doi: 10.1016/j.cbpa.2011.07.011. DOI: https://doi.org/10.1016/j.cbpa.2011.07.011

Xu Y, Goldkorn A. Telomere and telomerase therapeutics in cancer. Genes (Basel). 2016;7(6):22. doi: 10.3390/genes7060022. DOI: https://doi.org/10.3390/genes7060022

Stansel RM, de Lange T, Griffith JD. T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang. EMBO J. 2001;20(19):5532-5540. doi: 10.1093/emboj/20.19.5532. DOI: https://doi.org/10.1093/emboj/20.19.5532

de Lange T. Protection of mammalian telomeres. Oncogene. 2002;21(4):532-540. doi: 10.1038/sj.onc.1205080. DOI: https://doi.org/10.1038/sj.onc.1205080

de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005;19(18):2100-2110. doi: 10.1101/gad.1346005. DOI: https://doi.org/10.1101/gad.1346005

Palm W, de Lange T. How shelterin protects mammalian telomeres. Annu Rev Genet. 2008;42:301-334. doi: 10.1146/annurev.genet.41.110306.130350. DOI: https://doi.org/10.1146/annurev.genet.41.110306.130350

de Lange T. Shelterin-mediated telomere protection. Annu Rev Genet. 2018;52:223-247. doi: 10.1146/annurev-genet-032918-021921. DOI: https://doi.org/10.1146/annurev-genet-032918-021921

Bettin N, Oss Pegorar C, Cusanelli E. The emerging roles of TERRA in telomere maintenance and Genome Stability. Cells. 2019;8(3):246. doi: 10.3390/cells8030246. DOI: https://doi.org/10.3390/cells8030246

Nasheuer HP, Meaney AM. Starting DNA synthesis: Initiation processes during the replication of chromosomal DNA in humans. Genes (Basel). 2024;15(3):360. doi: 10.3390/genes15030360. DOI: https://doi.org/10.3390/genes15030360

Lundblad V. Telomere end processing: unexpected complexity at the end game. Genes Dev. 2012;26(11):1123-1127. doi: 10.1101/gad.195339.112. DOI: https://doi.org/10.1101/gad.195339.112

Okazaki R, Okazaki T, Sakabe K, Sugimoto K, Sugino A. Mechanism of DNA chain growth. I. Possible discontinuity and unusual secondary structure of newly synthesized chains. Proc Natl Acad Sci U S A. 1968;59(2):598-605. doi: 10.1073/pnas.59.2.598. DOI: https://doi.org/10.1073/pnas.59.2.598

Sugimoto K, Okazaki T, Okazaki R. Mechanism of DNA chain growth, II. Accumulation of newly synthesized short chains in E. coli infected with ligase-defective T4 phages. Proc Natl Acad Sci U S A. 1968;60(4):1356-62. doi: 10.1073/pnas.60.4.1356. DOI: https://doi.org/10.1073/pnas.60.4.1356

Burgers PMJ, Kunkel TA. Eukaryotic DNA replication fork. Annu Rev Biochem. 2017;86:417-438. doi: 10.1146/annurev-biochem-061516-044709. DOI: https://doi.org/10.1146/annurev-biochem-061516-044709

Watson JD. Origin of concatemeric T7 DNA. Nat New Biol. 1972;239(94):197-201. doi: 10.1038/newbio239197a0. DOI: https://doi.org/10.1038/newbio239197a0

Olovnikov AM. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol. 1973;41(1):181-190. doi: 10.1016/0022-5193(73)90198-7. DOI: https://doi.org/10.1016/0022-5193(73)90198-7

Sfeir AJ, Chai W, Shay JW, Wright WE. Telomere-end processing the terminal nucleotides of human chromosomes. Mol Cell. 2005;18(1):131-138. doi: 10.1016/j.molcel.2005.02.035. DOI: https://doi.org/10.1016/j.molcel.2005.02.035

Cai SW, de Lange T. CST-Polα/Primase: the second telomere maintenance machine. Genes Dev. 2023;37(13-14):555-569. doi: 10.1101/gad.350479.123. DOI: https://doi.org/10.1101/gad.350479.123

Wu P, Takai H, de Lange T. Telomeric 3' overhangs derive from resection by Exo1 and Apollo and fill-in by POT1b-associated CST. Cell. 2012;150(1):39-52. doi: 10.1016/j.cell.2012.05.026. DOI: https://doi.org/10.1016/j.cell.2012.05.026

Lenain C, Bauwens S, Amiard S, Brunori M, Giraud-Panis MJ, Gilson E. The Apollo 5' exonuclease functions together with TRF2 to protect telomeres from DNA repair. Curr Biol. 2006;16(13):1303-1310. doi: 10.1016/j.cub.2006.05.021. DOI: https://doi.org/10.1016/j.cub.2006.05.021

Lam YC, Akhter S, Gu P, Ye J, Poulet A, Giraud-Panis MJ, et al. SNMIB/Apollo protects leading-strand telomeres against NHEJ-mediated repair. EMBO J. 2010;29(13):2230-2241. doi: 10.1038/emboj.2010.58. DOI: https://doi.org/10.1038/emboj.2010.58

Wu P, van Overbeek M, Rooney S, de Lange T. Apollo contributes to G overhang maintenance and protects leading-end telomeres. Mol Cell. 2010;39(4):606-617. doi: 10.1016/j.molcel.2010.06.031. DOI: https://doi.org/10.1016/j.molcel.2010.06.031

Chow TT, Zhao Y, Mak SS, Shay JW, Wright WE. Early and late steps in telomere overhang processing in normal human cells: the position of the final RNA primer drives telomere shortening. Genes Dev. 2012;26(11):1167-1178. doi: 10.1101/gad.187211.112. DOI: https://doi.org/10.1101/gad.187211.112

Soudet J, Jolivet P, Teixeira MT. Elucidation of the DNA end-replication problem in Saccharomyces cerevisiae. Mol Cell. 2014;53(6):954-964. doi: 10.1016/j.molcel.2014.02.030. DOI: https://doi.org/10.1016/j.molcel.2014.02.030

Hockemeyer D, Collins K. Control of telomerase action at human telomeres. Nat Struct Mol Biol. 2015;22(11):848-852. doi: 10.1038/nsmb.3083. DOI: https://doi.org/10.1038/nsmb.3083

Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345(6274):458-460. doi: 10.1038/345458a0. DOI: https://doi.org/10.1038/345458a0

de Lange T, DePinho RA. Unlimited mileage from telomerase? Science. 1999;283(5404):947-949. doi: 10.1126/science.283.5404.947. DOI: https://doi.org/10.1126/science.283.5404.947

Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet. 2009;10:45-61. doi: 10.1146/annurev-genom-082908-150046. DOI: https://doi.org/10.1146/annurev-genom-082908-150046

Lai CK, Mitchell JR, Collins K. RNA binding domain of telomerase reverse transcriptase. Mol Cell Biol. 2001;21(4):990-1000. doi: 10.1128/MCB.21.4.990-1000.2001. DOI: https://doi.org/10.1128/MCB.21.4.990-1000.2001

Teixeira MT, Arneric M, Sperisen P, Lingner J. Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell. 2004;117(3):323-35. doi: 10.1016/s0092-8674(04)00334-4. DOI: https://doi.org/10.1016/S0092-8674(04)00334-4

Artandi SE, DePinho RA. Telomeres and telomerase in cancer. Carcinogenesis. 2010;31(1):9-18. doi: 10.1093/carcin/bgp268. DOI: https://doi.org/10.1093/carcin/bgp268

Baird DM, Rowson J, Wynford-Thomas D, Kipling D. Extensive allelic variation and ultrashort telomeres in senescent human cells. Nat Genet. 2003;33(2):203-207. doi: 10.1038/ng1084. DOI: https://doi.org/10.1038/ng1084

Zhao Y, Hoshiyama H, Shay JW, Wright WE. Quantitative telomeric overhang determination using a double-strand specific nuclease. Nucleic Acids Res. 2008;36(3):e14. doi: 10.1093/nar/gkm1063. DOI: https://doi.org/10.1093/nar/gkm1063

Aubert G. Telomere dynamics and aging. Prog Mol Biol Transl Sci. 2014;125:89-111. doi: 10.1016/B978-0-12-397898-1.00004-9. DOI: https://doi.org/10.1016/B978-0-12-397898-1.00004-9

Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999;97(4):527-38. doi: 10.1016/s0092-8674(00)80762-x. DOI: https://doi.org/10.1016/S0092-8674(00)80762-X

Preto A, Singhrao SK, Haughton MF, Kipling D, Wynford-Thomas D, Jones CJ. Telomere erosion triggers growth arrest but not cell death in human cancer cells retaining wild-type p53: implications for antitelomerase therapy. Oncogene. 2004;23(23):4136-4145. doi: 10.1038/sj.onc.1207564. DOI: https://doi.org/10.1038/sj.onc.1207564

Pickett HA, Reddel RR. Molecular mechanisms of activity and derepression of alternative lengthening of telomeres. Nat Struct Mol Biol. 2015;22(11):875-880. doi: 10.1038/nsmb.3106. DOI: https://doi.org/10.1038/nsmb.3106

Maciejowski J, de Lange T. Telomeres in cancer: tumour suppression and genome instability. Nat Rev Mol Cell Biol. 2017;18(3):175-186. doi: 10.1038/nrm.2016.171. DOI: https://doi.org/10.1038/nrm.2016.171

Hayashi MT, Cesare AJ, Fitzpatrick JA, Lazzerini-Denchi E, Karlseder J. A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nat Struct Mol Biol. 2012;19(4):387-394. doi: 10.1038/nsmb.2245. DOI: https://doi.org/10.1038/nsmb.2245

Hayashi MT, Cesare AJ, Rivera T, Karlseder J. Cell death during crisis is mediated by mitotic telomere deprotection. Nature. 2015;522(7557):492-496. doi: 10.1038/nature14513. DOI: https://doi.org/10.1038/nature14513

Sommerfeld HJ, Meeker AK, Piatyszek MA, Bova GS, Shay JW, Coffey DS. Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res. 1996;56(1):218-22.

Meeker AK, Hicks JL, Platz EA, March GE, Bennett CJ, Delannoy MJ, et al. Telomere shortening is an early somatic DNA alteration in human prostate tumorigenesis. Cancer Res. 2002;62(22):6405-6409.

Barthel FP, Wei W, Tang M, Martinez-Ledesma E, Hu X, Amin SB et al. Systematic analysis of telomere length and somatic alterations in 31 cancer types. Nat Genet. 2017;49(3):349-357. doi: 10.1038/ng.3781. DOI: https://doi.org/10.1038/ng.3781

Aviv A, Anderson JJ, Shay JW. Mutations, Cancer and the Telomere Length Paradox. Trends Cancer. 2017;3(4):253-258. doi: 10.1016/j.trecan.2017.02.005. DOI: https://doi.org/10.1016/j.trecan.2017.02.005

Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, et al. Inhibition of telomerase limits the growth of human cancer cells. Nat Med. 1999;5(10):1164-1170. doi: 10.1038/13495. DOI: https://doi.org/10.1038/13495

Seimiya H, Muramatsu Y, Ohishi T, Tsuruo T. Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics. Cancer Cell. 2005;7(1):25-37. doi: 10.1016/j.ccr.2004.11.021. DOI: https://doi.org/10.1016/j.ccr.2004.11.021

Fujiwara C, Muramatsu Y, Nishii M, Tokunaka K, Tahara H, Ueno M, et al. Cell-based chemical fingerprinting identifies telomeres and lamin A as modifiers of DNA damage response in cancer cells. Sci Rep. 2018;8(1):14827. doi: 10.1038/s41598-018-33139-x. DOI: https://doi.org/10.1038/s41598-018-33139-x

Deriano L, Roth DB. Modernizing the nonhomologous end-joining repertoire: alternative and classical NHEJ share the stage. Annu Rev Genet. 2013;47:433-455. doi: 10.1146/annurev-genet-110711-155540. DOI: https://doi.org/10.1146/annurev-genet-110711-155540

Shay JW. Role of Telomeres and Telomerase in Aging and Cancer. Cancer Discov. 2016;6(6):584-593. doi: 10.1158/2159-8290.CD-16-0062. DOI: https://doi.org/10.1158/2159-8290.CD-16-0062

Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, et al. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279(5349):349-352. doi: 10.1126/science.279.5349.349. DOI: https://doi.org/10.1126/science.279.5349.349

Feldser DM, Greider CW. Short telomeres limit tumor progression in vivo by inducing senescence. Cancer Cell. 2007;11(5):461-9. doi: 10.1016/j.ccr.2007.02.026. DOI: https://doi.org/10.1016/j.ccr.2007.02.026

Karlseder J, Smogorzewska A, de Lange T. Senescence induced by altered telomere state, not telomere loss. Science. 2002;295(5564):2446-2449. doi: 10.1126/science.1069523. DOI: https://doi.org/10.1126/science.1069523

Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266(5193):2011-2015. doi: 10.1126/science.7605428. DOI: https://doi.org/10.1126/science.7605428

Hayflick L. The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 1965;37:614-636. doi: 10.1016/0014-4827(65)90211-9. DOI: https://doi.org/10.1016/0014-4827(65)90211-9

Okamoto K, Seimiya H. Revisiting Telomere Shortening in Cancer. Cells. 2019;8(2):107. doi: 10.3390/cells8020107. DOI: https://doi.org/10.3390/cells8020107

Dratwa M, Wysoczańska B, Łacina P, Kubik T, Bogunia-Kubik K. TERT-Regulation and Roles in Cancer Formation. Front Immunol. 2020;11:589929. doi: 10.3389/fimmu.2020.589929. DOI: https://doi.org/10.3389/fimmu.2020.589929

Srinivas N, Rachakonda S, Kumar R. Telomeres and Telomere Length: A General Overview. Cancers (Basel). 2020;12(3):558. doi: 10.3390/cancers12030558. DOI: https://doi.org/10.3390/cancers12030558

Holesova Z, Krasnicanova L, Saade R, Pös O, Budis J, Gazdarica J, et al. Telomere length changes in cancer: Insights on carcinogenesis and potential for non-invasive diagnostic strategies. Genes (Basel). 2023;14(3):715. doi: 10.3390/genes14030715. DOI: https://doi.org/10.3390/genes14030715

De Vitis M, Berardinelli F, Sgura A. Telomere length maintenance in cancer: At the crossroad between telomerase and alternative lengthening of telomeres (ALT). Int J Mol Sci. 2018;19(2):606. doi: 10.3390/ijms19020606. DOI: https://doi.org/10.3390/ijms19020606

Guterres AN, Villanueva J. Targeting telomerase for cancer therapy. Oncogene. 2020;39(36):5811-5824. doi: 10.1038/s41388-020-01405-w. DOI: https://doi.org/10.1038/s41388-020-01405-w

Armanios M, Greider CW. Treating myeloproliferation--on target or off? N Engl J Med. 2015;373(10):965-966. doi: 10.1056/NEJMe1508740. DOI: https://doi.org/10.1056/NEJMe1508740

Trybek T, Kowalik A, Góźdź S, Kowalska A. Telomeres and telomerase in oncogenesis. Oncol Lett. 2020;20(2):1015-1027. doi: 10.3892/ol.2020.11659. DOI: https://doi.org/10.3892/ol.2020.11659

Asai A, Oshima Y, Yamamoto Y, Uochi TA, Kusaka H, Akinaga S, et al. A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res. 2003;63(14):3931-3939.

Vertecchi E, Rizzo A, Salvati E. Telomere targeting approaches in cancer: Beyond length maintenance. Int J Mol Sci. 2022;23(7):3784. doi: 10.3390/ijms23073784. DOI: https://doi.org/10.3390/ijms23073784

Chiappori AA, Kolevska T, Spigel DR, Hager S, Rarick M, Gadgeel S, et al. A randomized phase II study of the telomerase inhibitor imetelstat as maintenance therapy for advanced non-small-cell lung cancer. Ann Oncol. 2015;26(2):354-362. doi: 10.1093/annonc/mdu550. DOI: https://doi.org/10.1093/annonc/mdu550

Pascolo E, Wenz C, Lingner J, Hauel N, Priepke H, Kauffmann I, et al. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate. J Biol Chem. 2002;277(18):15566-15572. doi: 10.1074/jbc.M201266200. DOI: https://doi.org/10.1074/jbc.M201266200

Damm K, Hemmann U, Garin-Chesa P, Hauel N, Kauffmann I, Priepke H, et al. A highly selective telomerase inhibitor limiting human cancer cell proliferation. EMBO J. 2001;20(24):6958-6968. doi: 10.1093/emboj/20.24.6958. DOI: https://doi.org/10.1093/emboj/20.24.6958

El-Daly H, Kull M, Zimmermann S, Pantic M, Waller CF, Martens UM. Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532. Blood. 2005;105(4):1742-1749. doi: 10.1182/blood-2003-12-4322. DOI: https://doi.org/10.1182/blood-2003-12-4322

Biffi G, Tannahill D, McCafferty J, Balasubramanian S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nat Chem. 2013;5(3):182-186. doi: 10.1038/nchem.1548. DOI: https://doi.org/10.1038/nchem.1548

Drosopoulos WC, Kosiyatrakul ST, Schildkraut CL. BLM helicase facilitates telomere replication during leading strand synthesis of telomeres. J Cell Biol. 2015;210(2):191-208. doi: 10.1083/jcb.201410061. DOI: https://doi.org/10.1083/jcb.201410061

Tauchi T, Shin-ya K, Sashida G, Sumi M, Okabe S, Ohyashiki JH, et al. Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia. Oncogene. 2006;25(42):5719-5725. doi: 10.1038/sj.onc.1209577. DOI: https://doi.org/10.1038/sj.onc.1209577

Huppert JL, Balasubramanian S. Prevalence of quadruplexes in the human genome. Nucleic Acids Res. 2005;33(9):2908-2916. doi: 10.1093/nar/gki609. DOI: https://doi.org/10.1093/nar/gki609

Ivancich M, Schrank Z, Wojdyla L, Leviskas B, Kuckovic A, Sanjali A, et al. Treating Cancer by Targeting Telomeres and Telomerase. Antioxidants (Basel). 2017;6(1):15. doi: 10.3390/antiox6010015. DOI: https://doi.org/10.3390/antiox6010015

Spiegel J, Adhikari S, Balasubramanian S. The structure and function of DNA G-quadruplexes. Trends Chem. 2020;2(2):123-136. doi: 10.1016/j.trechm.2019.07.002. DOI: https://doi.org/10.1016/j.trechm.2019.07.002

Pagano A, Iaccarino N, Abdelhamid MAS, Brancaccio D, Garzarella EU, Di Porzio A, et al. Common G-quadruplex binding agents found to interact with i-motif-forming DNA: Unexpected multi-target-directed compounds. Front Chem. 2018;6:281. doi: 10.3389/fchem.2018.00281. DOI: https://doi.org/10.3389/fchem.2018.00281

Sengupta S, Sobo M, Lee K, Senthil Kumar S, White AR, Mender I et al. Induced Telomere Damage to Treat Telomerase Expressing Therapy-Resistant Pediatric Brain Tumors. Mol Cancer Ther. 2018;17(7):1504-1514. doi: 10.1158/1535-7163.MCT-17-0792. DOI: https://doi.org/10.1158/1535-7163.MCT-17-0792

Mender I, Gryaznov S, Dikmen ZG, Wright WE, Shay JW. Induction of telomere dysfunction mediated by the telomerase substrate precursor 6-thio-2'-deoxyguanosine. Cancer Discov. 2015;5(1):82-95. doi: 10.1158/2159-8290.CD-14-0609. DOI: https://doi.org/10.1158/2159-8290.CD-14-0609

Zhang G, Wu LW, Mender I, Barzily-Rokni M, Hammond MR, Ope O, et al. Induction of telomere dysfunction prolongs disease control of therapy-resistant melanoma. Clin Cancer Res. 2018;24(19):4771-4784. doi: 10.1158/1078-0432.CCR-17-2773. DOI: https://doi.org/10.1158/1078-0432.CCR-17-2773

Zeng X, Hernandez-Sanchez W, Xu M, Whited TL, Baus D, Zhang J, et al. Administration of a nucleoside analog promotes cancer cell death in a telomerase-dependent manner. Cell Rep. 2018;23(10):3031-3041. doi: 10.1016/j.celrep.2018.05.020. DOI: https://doi.org/10.1016/j.celrep.2018.05.020

Chiba K, Johnson JZ, Vogan JM, Wagner T, Boyle JM, Hockemeyer D. Cancer-associated TERT promoter mutations abrogate telomerase silencing. Elife. 2015;4:e07918. doi: 10.7554/eLife.07918. DOI: https://doi.org/10.7554/eLife.07918

Kinde I, Munari E, Faraj SF, Hruban RH, Schoenberg M, Bivalacqua T, et al. TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. Cancer Res. 2013;73(24):7162-7167. doi: 10.1158/0008-5472.CAN-13-2498. DOI: https://doi.org/10.1158/0008-5472.CAN-13-2498

Ludlow AT, Wong MS, Robin JD, Batten K, Yuan L, Lai TP, et al. NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer. Nat Commun. 2018;9(1):3112. doi: 10.1038/s41467-018-05582-x. DOI: https://doi.org/10.1038/s41467-018-05582-x

Zanetti M. A second chance for telomerase reverse transcriptase in anticancer immunotherapy. Nat Rev Clin Oncol. 2017;14(2):115-128. doi: 10.1038/nrclinonc.2016.67. DOI: https://doi.org/10.1038/nrclinonc.2016.67

Lilleby W, Gaudernack G, Brunsvig PF, Vlatkovic L, Schulz M, Mills K, et al. Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer. Cancer Immunol Immunother. 2017;66(7):891-901. doi: 10.1007/s00262-017-1994-y. DOI: https://doi.org/10.1007/s00262-017-1994-y

Staff C, Mozaffari F, Frödin JE, Mellstedt H, Liljefors M. Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients. Int J Oncol. 2014;45(3):1293-303. doi: 10.3892/ijo.2014.2496. DOI: https://doi.org/10.3892/ijo.2014.2496

Fenoglio D, Parodi A, Lavieri R, Kalli F, Ferrera F, Tagliamacco A, et al. Immunogenicity of GX301 cancer vaccine: Four (telomerase peptides) are better than one. Hum Vaccin Immunother. 2015;11(4):838-850. doi: 10.1080/21645515.2015.1012032. DOI: https://doi.org/10.1080/21645515.2015.1012032

Al-Janabi I. Response Challenges to Cancer Immunotherapies. Al-Rafidain J Med Sci. 2022;2:51–80. doi: 10.54133/ajms.v2i.65. DOI: https://doi.org/10.54133/ajms.v2i.65

Sandri S, Bobisse S, Moxley K, Lamolinara A, De Sanctis F, Boschi F, et al. Feasibility of telomerase-specific adoptive T-cell therapy for B-cell chronic lymphocytic leukemia and solid malignancies. Cancer Res. 2016;76(9):2540-2551. doi: 10.1158/0008-5472.CAN-15-2318. DOI: https://doi.org/10.1158/0008-5472.CAN-15-2318

Su Z, Dannull J, Yang BK, Dahm P, Coleman D, Yancey D, et al. Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol. 2005;174(6):3798-3807. doi: 10.4049/jimmunol.174.6.3798. DOI: https://doi.org/10.4049/jimmunol.174.6.3798

Yan J, Pankhong P, Shin TH, Obeng-Adjei N, Morrow MP, Walters JN, et al. Highly optimized DNA vaccine targeting human telomerase reverse transcriptase stimulates potent antitumor immunity. Cancer Immunol Res. 2013;1(3):179-189. doi: 10.1158/2326-6066.CIR-13-0001. DOI: https://doi.org/10.1158/2326-6066.CIR-13-0001

Thalmensi J, Pliquet E, Liard C, Escande M, Bestetti T, Julithe M, et al. Anticancer DNA vaccine based on human telomerase reverse transcriptase generates a strong and specific T cell immune response. Oncoimmunology. 2015;5(3):e1083670. doi: 10.1080/2162402X.2015.1083670. DOI: https://doi.org/10.1080/2162402X.2015.1083670

Nemunaitis J, Tong AW, Nemunaitis M, Senzer N, Phadke AP, Bedell C, et al. A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol Ther. 2010;18(2):429-434. doi: 10.1038/mt.2009.262. DOI: https://doi.org/10.1038/mt.2009.262

Kanaya N, Kuroda S, Morihiro T, Kakiuchi Y, Kubota T, Kakiuchi S, et al. Abstract 2744:Telomelysin-induced immunogenic cell death synergizes with anti-PD-1 antibody in nonimmunogenic gastrointestinal tumors. Cancer Res. 2018;78:2744–274. doi: 10.1038/s41388-020-01405-w. DOI: https://doi.org/10.1158/1538-7445.AM2018-2744

Schrank Z, Khan N, Osude C, Singh S, Miller RJ, Merrick C, et al. Oligonucleotides Targeting Telomeres and Telomerase in Cancer. Molecules. 2018;23(9):2267. doi: 10.3390/molecules23092267. DOI: https://doi.org/10.3390/molecules23092267

Bejarano L, Schuhmacher AJ, Méndez M, Megías D, Blanco-Aparicio C, Martínez S, et al. Inhibition of TRF1 telomere protein impairs tumor initiation and progression in glioblastoma mouse models and patient-derived xenografts. Cancer Cell. 2017;32(5):590-607.e4. doi: 10.1016/j.ccell.2017.10.006. DOI: https://doi.org/10.1016/j.ccell.2017.10.006

Sánchez-Vázquez R, Martínez P, Blasco MA. AKT-dependent signaling of extracellular cues through telomeres impact on tumorigenesis. PLoS Genet. 2021;17(3):e1009410. doi: 10.1371/journal.pgen.1009410. DOI: https://doi.org/10.1371/journal.pgen.1009410

Cook BD, Dynek JN, Chang W, Shostak G, Smith S. Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Mol Cell Biol. 2002;22(1):332-342. doi: 10.1128/MCB.22.1.332-342.2002. DOI: https://doi.org/10.1128/MCB.22.1.332-342.2002

Riffell JL, Lord CJ, Ashworth A. Tankyrase-targeted therapeutics: expanding opportunities in the PARP family. Nat Rev Drug Discov. 2012;11(12):923-936. doi: 10.1038/nrd3868. DOI: https://doi.org/10.1038/nrd3868

Biroccio A, Cherfils-Vicini J, Augereau A, Pinte S, Bauwens S, Ye J, et al. TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells. Nat Cell Biol. 2013;15(7):818-828. doi: 10.1038/ncb2774. DOI: https://doi.org/10.1038/ncb2774

Zizza P, Dinami R, Porru M, Cingolani C, Salvati E, Rizzo A, et al. TRF2 positively regulates SULF2 expression increasing VEGF-A release and activity in tumor microenvironment. Nucleic Acids Res. 2019;47(7):3365-3382. doi: 10.1093/nar/gkz041. DOI: https://doi.org/10.1093/nar/gkz041

Chen X, Liu L, Chen Y, Yang Y, Yang CY, Guo T, et al. Cyclic peptidic mimetics of apollo peptides targeting telomeric repeat binding factor 2 (TRF2) and apollo interaction. ACS Med Chem Lett. 2018;9(5):507-511. doi: 10.1021/acsmedchemlett.8b00152. DOI: https://doi.org/10.1021/acsmedchemlett.8b00152

Wu Y, Poulos RC, Reddel RR. Role of POT1 in Human Cancer. Cancers (Basel). 2020;12(10):2739. doi: 10.3390/cancers12102739. DOI: https://doi.org/10.3390/cancers12102739

Altschuler SE, Croy JE, Wuttke DS. A small molecule inhibitor of Pot1 binding to telomeric DNA. Biochemistry. 2012;51(40):7833-7845. doi: 10.1021/bi300365k. DOI: https://doi.org/10.1021/bi300365k

Dinami R, Ercolani C, Petti E, Piazza S, Ciani Y, Sestito R, et al. miR-155 drives telomere fragility in human breast cancer by targeting TRF1. Cancer Res. 2014;74(15):4145-4156. doi: 10.1158/0008-5472.CAN-13-2038. DOI: https://doi.org/10.1158/0008-5472.CAN-13-2038

Luo Z, Feng X, Wang H, Xu W, Zhao Y, Ma W, et al. Mir-23a induces telomere dysfunction and cellular senescence by inhibiting TRF2 expression. Aging Cell. 2015;14(3):391-399. doi: 10.1111/acel.12304. DOI: https://doi.org/10.1111/acel.12304

Li T, Luo Z, Lin S, Li C, Dai S, Wang H, et al. MiR-185 targets POT1 to induce telomere dysfunction and cellular senescence. Aging (Albany NY). 2020;12(14):14791-14807. doi: 10.18632/aging.103541. DOI: https://doi.org/10.18632/aging.103541

Kang S, Cao J, Zhang M, Li X, Guo QL, Zeng H, et al. Transcriptional regulation of telomeric repeat-containing RNA by acridine derivatives. RNA Biol. 2021;18(12):2261-2277. doi: 10.1080/15476286.2021.1899652. DOI: https://doi.org/10.1080/15476286.2021.1899652

Downloads

Published

2025-01-09

How to Cite

Al-Janabi, I. I. (2025). Telomere Length and Cancer. Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 ), 8(1), 14–22. https://doi.org/10.54133/ajms.v8i1.1615

Issue

Section

Review article

Similar Articles

1 2 3 4 5 > >> 

You may also start an advanced similarity search for this article.