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Telomerase and cancer therapeutics

Nature reviews. Cancer, v.8 no.3, 2008년, pp.167 - 179  

Harley, Calvin B. (Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA. CHarley@Geron.com)

Abstract AI-Helper 아이콘AI-Helper

Telomerase is an attractive cancer target as it appears to be required in essentially all tumours for immortalization of a subset of cells, including cancer stem cells. Moreover, differences in telomerase expression, telomere length and cell kinetics between normal and tumour tissues suggest that ta...

참고문헌 (143)

  1. Cell JD Hanahan 100 57 2000 10.1016/S0092-8674(00)81683-9 Hanahan, J. D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57-70 (2000). 

  2. Cold Spring Harbor Symp. Quant. Biol. CB Harley 59 307 1994 10.1101/SQB.1994.059.01.035 Harley, C. B. et al. Telomerase, cell immortality, and cancer. Cold Spring Harbor Symp. Quant. Biol. 59, 307-315 (1994). 

  3. Nature Med. WC Hahn 5 1164 1999 10.1038/13495 Hahn, W. C. et al. Inhibition of telomerase limits the growth of human cancer cells. Nature Med. 5, 1164-1170 (1999). 

  4. Clin. Cancer Res. L Kelland 13 4960 2007 10.1158/1078-0432.CCR-07-0422 Kelland, L. Targeting the limitless replicative potential of cancer: the telomerase/telomere pathway. Clin. Cancer Res. 13, 4960-4963 (2007). 

  5. Cell CW Greider 51 405 1985 10.1016/0092-8674(85)90170-9 Greider, C. W. & Blackburn, E. H. Identification of a specific telomere terminal transferase enzyme with two kinds of primer specificity. Cell 51, 405-413 (1985). The discovery of the biochemical activity of telomerase is reported in a protozoan, enabling future work on the role of telomeres and telomerase in human ageing and cancer. 

  6. Nature CW Greider 337 331 1989 10.1038/337331a0 Greider, C. W. & Blackburn, E. H. A telomeric sequence in the RNA of tetrahymena telomerase required for telomere repeat synthesis. Nature 337, 331-337 (1989). 

  7. J. Biol. Chem. D Liu 279 51338 2004 10.1074/jbc.M409293200 Liu, D., O'Connor, M. S., Qin, J. & Songyang, Z. Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins. J. Biol. Chem. 279, 51338-51342 (2004). 

  8. Genes Dev. T de Lange 19 2100 2005 10.1101/gad.1346005 de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100-2110 (2005). In this and the preceding reference, the collection of telomere-binding proteins is put into an emerging structure for the chromosome tip, the 'telosome' or 'shelterin', and potential interactions with telomerase are summarized. 

  9. Nature CB Harley 345 458 1990 10.1038/345458a0 Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460 (1990). The association between telomere loss and replicative ageing in normal human somatic cells is first reported. 

  10. Nature ND Hastie 346 866 1990 10.1038/346866a0 Hastie, N. D. et al. Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866-868 (1990). The first broad survey of telomere lengths in pre-malignant and malignant tumour samples finds short telomeres in malignant cancer tissue. 

  11. Cell RJ Wellinger 16 3094 1996 Wellinger, R. J., Ethier, K., Labrecque, P. & Zakian, V. A. Evidence for a new step in telomere maintenance. Cell 16, 3094-3105 (1996). 

  12. Mol. Cell NK Jacob 11 1021 2003 10.1016/S1097-2765(03)00131-X Jacob, N. K., Kirk, K. E. & Price, C. M. Generation of telomeric G strand overhangs involves both G and C strand cleavage. Mol. Cell 11, 1021-1032 (2003). 

  13. Cancer Res. A Goldkorn 66 5763 2006 10.1158/0008-5472.CAN-05-3782 Goldkorn, A. & Blackburn, E. H. Assembly of mutant-template telomerase RNA into catalytically active telomerase ribonucleoprotein that can act on telomeres is required for apoptosis and cell cycle arrest in human cancer cells. Cancer Res. 66, 5763-5771 (2006). 

  14. Dev. Genet. WE Wright 18 173 1996 10.1002/(SICI)1520-6408(1996)18:2<173::AID-DVG10>3.0.CO;2-3 Wright, W. E., Piatyszek, M. A., Rainey, W. E., Byrd, W. & Shay, J. W. Telomerase activity in human germline and embryonic tissues and cells. Dev. Genet. 18, 173-179 (1996). 

  15. Cancer Res. GA Ulaner 58 4168 1998 Ulaner, G. A., Hu, J.-F., Vu, T. H., Giudice, L. C. & Hoffman, A. R. Telomerase activity in human development is regulated both by hTERT transcription and by alternate splicing of hTERT transcripts. Cancer Res. 58, 4168-4172 (1998). 

  16. Biochem. Biophys. Res. Comm. S Kakuo 263 308 1999 10.1006/bbrc.1999.1385 Kakuo, S., Asaoka, K. & Ide, T. Human is a unique species among primates in terms of telomere length. Biochem. Biophys. Res. Comm. 263, 308-314 (1999). 

  17. Exp. Cell Res. S Steinert 272 146 2002 10.1006/excr.2001.5409 Steinert, S., White, D., Zou, Y., Shay, J. W. & Wright, W. E. Telomere biology and cellular aging in non-human primate cells. Exp. Cell Res. 272, 146-152 (2002). 

  18. Pediatr. Res. K Okuda 52 377 2002 10.1203/00006450-200209000-00012 Okuda, K. et al. Telomere length in the newborn. Pediatr. Res. 52, 377-381 (2002). 

  19. Exp. Cell Res. A Bodnar 228 58 1996 10.1006/excr.1996.0299 Bodnar, A., Kim, N. W., Effros, R. B. & Chiu, C.-P. Mechanism of telomerase induction during T cell activation. Exp. Cell Res. 228, 58-64 (1996). 

  20. Proc. Natl Acad. Sci. D Broccoli 92 9082 1995 10.1073/pnas.92.20.9082 Broccoli, D., Young, J. W. & de Lange, T. Telomerase activity in normal and malignant hematopoietic cells. Proc. Natl Acad. Sci. 92, 9082-9086 (1995). 

  21. Stem Cells CP Chiu 14 239 1996 10.1002/stem.140239 Chiu, C. P. et al. Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells 14, 239-248 (1996). 

  22. Mut. Res. CB Harley 256 271 1991 10.1016/0921-8734(91)90018-7 Harley, C. B. Telomere loss: mitotic clock or genetic time bomb? Mut. Res. 256, 271-282 (1991). 

  23. EMBO J. CM Counter 11 1921 1992 10.1002/j.1460-2075.1992.tb05245.x Counter, C. M. et al. Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J. 11, 1921-1929 (1992). Critically shortened telomeres in a model of cell transformation and immortalization are shown to be linked to genetic rearrangements that are stabilized when telomerase is activated. 

  24. Cell RA Greenberg 97 515 1999 10.1016/S0092-8674(00)80761-8 Greenberg, R. A. et al. Short dysfunctional telomeres impair tumorigenesis in the INK4aD2/3 cancer-prone mouse. Cell 97, 515-525 (1999). 

  25. Nature D Hanahan 406 573 2000 10.1038/35020662 Hanahan, D. Benefits of bad telomeres. Nature 406, 573-574 (2000). 

  26. Oncogene CB Harley 21 494 2002 10.1038/sj.onc.1205076 Harley, C. B. Telomerase is not an oncogene. Oncogene 21, 494-502 (2002). 

  27. Proc. Natl Acad. Sci. USA CM Khoo 104 3931 2007 10.1073/pnas.0700093104 Khoo, C. M., Carrasco, D. R., Bosenberg, M. W., Paik, J.-H. & DePinho, R. A. Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse. Proc. Natl Acad. Sci. USA 104, 3931-3936 (2007). 

  28. Lancet RM Cawthon 361 359 2003 10.1016/S0140-6736(03)12384-7 Cawthon, R. M., Smith, K. R., O'Brien, E., Sivatchenko, A. & Kerber, R. A. Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361, 359-395 (2003). A simple and rapid telomere length assay developed by the lead author is used in a human epidemiology study, demonstrating increased mortality risk of cancer in individuals with short telomeres. 

  29. Proc. Natl Acad. Sci. ES Epel 101 17312 2004 10.1073/pnas.0407162101 Epel, E. S. et al. Accelerated telomere shortening in response to life stress. Proc. Natl Acad. Sci. 101, 17312-17315 (2004). 

  30. Hypertension A Benetos 43 182 2004 10.1161/01.HYP.0000113081.42868.f4 Benetos, A. et al. Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects. Hypertension 43, 182-185 (2004). 

  31. Nature Genet. T Vulliamy 36 447 2004 10.1038/ng1346 Vulliamy, T. et al. Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nature Genet. 36, 447-449 (2004). 

  32. Int. J. Hematol. A Walne 82 184 2005 10.1532/IJH97.05067 Walne, A., Marrone, A. & Dokal, I. Dyskeratosis congenita: a disorder of defective telomere maintenance? Int. J. Hematol. 82, 184-189 (2005). 

  33. Aging Cell S Demissle 5 325 2006 10.1111/j.1474-9726.2006.00224.x Demissle, S. et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 5, 325-330 (2006). 

  34. Am. J. Epidemiol. AL Fitzpatrick 165 14 2007 10.1093/aje/kwj346 Fitzpatrick, A. L. et al. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am. J. Epidemiol. 165, 14-21 (2007). 

  35. Lancet SW Brouilette 369 107 2007 10.1016/S0140-6736(07)60071-3 Brouilette, S. W. et al. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 369, 107-114 (2007). 

  36. N. Engl. J. Med. MY Armanios 356 1370 2007 10.1056/NEJMoa066157 Armanios, M. Y. et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N. Engl. J. Med. 356, 1370-1372 (2007). 

  37. Science NW Kim 266 2011 1994 10.1126/science.7605428 Kim, N. W. et al. Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011-2014 (1994). A highly sensitive PCR assay for telomerase activity (TRAP) is reported, enabling detection of telomerase in a broad range of tumour cell lines and in certain normal cells. 

  38. Eur. J. Cancer JW Shay 33 787 1997 10.1016/S0959-8049(97)00062-2 Shay, J. W. & Bacchetti, S. A survey of telomerase activity in human cancer. Eur. J. Cancer 33, 787-791 (1997). 

  39. Nat. Clin. Pract. Oncol. WN Keith 1 88 2004 10.1038/ncponc0044 Keith, W. N., Bilsland, A., Hardie, M. & Evans, T. R. Drug Insight: cancer cell immortality - telomerase as a target for novel cancer gene therapies. Nat. Clin. Pract. Oncol. 1, 88-96 (2004). 

  40. Cell. Mol. Life Sci. S Zimmermann 64 906 2007 10.1007/s00018-007-6481-8 Zimmermann, S. & Martens, U. M. Telomeres and telomerase as targets for cancer therapy Cell. Mol. Life Sci. 64 906-921 (2007). 

  41. 10.1038/sj.bjp.0707374 Phatak, P. & Burger, A. M. Telomerase and its potential for therapeutic intervention. Br. J. Pharmacol. (2007). 

  42. Nature T Finkel 448 767 2007 10.1038/nature05985 Finkel, T., S. M. & Blasco, M. A. The common biology of cancer and ageing. Nature 448, 767-774 (2007). 

  43. Nature Chem. Biol. MA Blasco 3 640 2007 10.1038/nchembio.2007.38 Blasco, M. A. Telomere length, stem cells and aging. Nature Chem. Biol. 3, 640-649 (2007). 

  44. BioEssays CW Greider 12 363 1990 10.1002/bies.950120803 Greider, C. W. Telomeres, telomerase and senescence. BioEssays 12, 363-368 (1990). 

  45. Science J Feng 269 1236 1995 10.1126/science.7544491 Feng, J. et al. The RNA component of human telomerase. Science 269, 1236-1241 (1995). The RNA component of human telomerase is cloned and characterized, enabling specific modulation of telomerase activity and facilitating the discovery of telomerase inhibitors targeting the RNA template region of telomerase. 

  46. Science TM Nakamura 277 955 1997 10.1126/science.277.5328.955 Nakamura, T. M. et al. Telomerase catalytic subunit homologs from fission yeast and human. Science 277, 955-959 (1997). The catalytic protein component of human telomerase (TERT) is cloned, enabling further experimental manipulation of telomerase in normal and tumour tissues, and the development of the first telomerase-based drugs (TERT vaccines) to enter clinical trials. 

  47. Cell M Meyerson 90 785 1997 10.1016/S0092-8674(00)80538-3 Meyerson, M. et al. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90, 785-795 (1997). 

  48. Genes Dev. L Harrington 11 3109 1997 10.1101/gad.11.23.3109 Harrington, L. et al. Human telomerase contains evolutionarily conserved catalytic and structural subunits. Genes Dev. 11, 3109-3115 (1997). 

  49. Nature Genet. SL Weinrich 17 498 1997 10.1038/ng1297-498 Weinrich, S. L. et al. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Nature Genet. 17, 498-502 (1997). 

  50. Hum. Mol. Genet. A Kilian 6 2011 1997 10.1093/hmg/6.12.2011 Kilian, A. et al. Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types. Hum. Mol. Genet. 6, 2011-2019 (1997). 

  51. Nature Genet. J-I Nakayama 18 65 1998 10.1038/ng0198-65 Nakayama, J.-I. et al. Telomerase activation by hTRT in human normal fibroblasts and hepatocellular carcinomas. Nature Genet. 18, 65-68 (1998). 

  52. J. Transl. Med. X Cortez-Gonzalez 5 12 2007 10.1186/1479-5876-5-12 Cortez-Gonzalez, X. & Zanetti, M. Telomerase immunity from bench to bedside: round one. J. Transl. Med. 5, 12 (2007). 

  53. Anticancer Agents Med. Chem. J Fakhoury 7 475 2007 10.2174/187152007781058622 Fakhoury, J., Nimmo, G. A. & Autexier, C. Harnessing telomerase in cancer therapeutics. Anticancer Agents Med. Chem. 7, 475-483 (2007). 

  54. Cancer Lett. E Hiyama 194 221 2003 10.1016/S0304-3835(02)00709-7 Hiyama, E. & Hiyama, K. Telomerase as tumor marker. Cancer Lett. 194, 221-233 (2003). 

  55. Cold Spring Harb. Symp. Quant. Biol. M Armanios 70 205 2005 10.1101/sqb.2005.70.030 Armanios, M. & Greider, C. W. Telomerase and cancer stem cells. Cold Spring Harb. Symp. Quant. Biol. 70, 205-208 (2005). 

  56. Cancer Res. MM Ho 67 4827 2007 10.1158/0008-5472.CAN-06-3557 Ho, M. M., Nq, A. V., Lam, S. & Hung., J. Y. Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells. Cancer Res. 67, 4827-4833 (2007). 

  57. Br. J. Cancer P Phatak 96 1223 2007 10.1038/sj.bjc.6603691 Phatak, P. et al. Telomere uncapping by the G-quadruplex ligand RHPS4 inhibits clonogenic tumour cell growth in vitro and in vivo consistent with a cancer stem cell targeting mechanism. Br. J. Cancer 96, 1223-1233 (2007). 

  58. Clin. Cancer Res. ER Camp 11 397 2005 10.1158/1078-0432.397.11.1 Camp, E. R. et al. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor. Clin. Cancer Res. 11, 397-405 (2005). 

  59. Oncogene AE Bilsland 22 370 2003 10.1038/sj.onc.1206168 Bilsland, A. E. et al. Selective ablation of human cancer cells by telomerase-specific adenoviral suicide gene therapy vectors expressing bacterial nitroreductase. Oncogene 22, 370-380 (2003). In vivo proof of concept using a prodrug suicide gene approach driven by either the hTR or the TERT promoter in a non-oncolytic adenoviral vector. 

  60. Clin. Cancer Res. Q Zhang 12 6523 2006 10.1158/1078-0432.CCR-06-1491 Zhang, Q. et al. Increased safety with preserved antitumoral efficacy on hepatocellular carcinoma with dual-regulated oncolytic adenovirus. Clin. Cancer Res. 12, 6523-6531 (2006). 

  61. Cancer Gene Ther. J Irving 11 174 2004 10.1038/sj.cgt.7700666 Irving, J. et al. Conditionally replicative adenovirus driven by the human telomerase promoter provides broad-spectrum antitumor activity without liver toxicity. Cancer Gene Ther. 11, 174-185 (2004). In vivo proof of concept and demonstration of safety for a conditional replicative oncolytic virus driven by the TERT promoter. 

  62. J. Biol. Chem. S Li 280 23709 2005 10.1074/jbc.M502782200 Li, S., Crothers, J., Haqq, C. M. & Blackburn, E. H. Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depletion of telomerase RNA. J. Biol. Chem. 280, 23709-23717 (2005). 

  63. Mol. Cell. L Xu 28 315 2007 10.1016/j.molcel.2007.10.005 Xu, L. & Blackburn, E. H. Human cancer cells harbor T-stumps, a distinct class of extremely short telomeres. Mol. Cell. 28, 315-327 (2007). 

  64. J. Mol. Biol. SM Haider 326 117 2003 10.1016/S0022-2836(02)01354-2 Haider, S. M., Parkinson, G. N. & Neidle, S. Structure of a G-quadruplex-ligand complex. J. Mol. Biol. 326, 117-125 (2003). 

  65. Nucl. Acids Res. D Patel 35 7429 2007 10.1093/nar/gkm711 Patel, D., Phan, A. & Kuryavyi, V. Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics. Nucl. Acids Res. 35, 7429-7455 (2007). 

  66. Mol. Pharmacol. S Gowan 61 1154 2002 10.1124/mol.61.5.1154 Gowan, S. et al. A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity. Mol. Pharmacol. 61, 1154-1162 (2002). 

  67. Biochem. Pharmacol. M Gunaratnam 74 679 2007 10.1016/j.bcp.2007.06.011 Gunaratnam, M. et al. Mechanism of acridine-based telomerase inhibition and telomere shortening. Biochem. Pharmacol. 74, 679-689 (2007). 

  68. J. Clin. Invest. E Salvati 117 3236 2007 10.1172/JCI32461 Salvati, E. et al. Telomere damage induced by the G-quadruplex ligand RHPS4 has an antitumor effect. J. Clin. Invest. 117, 3236-3247 (2007). In vivo proof of concept for a late preclinical drug candidate targeting the telomere. 

  69. Bioessays L Oganesian 29 155 2007 10.1002/bies.20523 Oganesian, L. & Bryan, T. Physiological relevance of telomeric G-quadruplex formation: a potential drug target. Bioessays 29, 155-165 (2007). 

  70. J. Biol. Chem. E Pascolo 277 15566 2002 10.1074/jbc.M201266200 Pascolo, E. et al. Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate. J. Biol. Chem. 277, 15566-15572 (2002). 

  71. Mol. Pharmacol. RJ Ward 68 779 2005 10.1124/mol.105.011494 Ward, R. J. & Autexier, C. Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment. Mol. Pharmacol. 68, 779-786 (2005). 

  72. Bioorg. Med. Chem. Lett. DK Barma 13 1333 2003 10.1016/S0960-894X(03)00101-X Barma, D. K., Elayadi, A., Falck, J. R. & Corey, D. R. Inhibition of telomerase by BIBR 1532 and related analogues. Bioorg. Med. Chem. Lett. 13, 1333-1336 (2003). 

  73. Lab. Invest. K Piotrowska 85 1565 2005 10.1038/labinvest.3700352 Piotrowska, K. et al. Optimization of the TRAP assay to evaluate specificity of telomerase inhibitors. Lab. Invest. 85, 1565-1569 (2005). Care must be taken in using the standard PCR-based TRAP assay for evaluation of telomerase inhibitors. 

  74. Nature Med. S Zhou 7 1028 2001 10.1038/nm0901-1028 Zhou, S. et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nature Med. 7, 1028-1034 (2001). 

  75. Cancer Res. A Asai 63 3931 2003 Asai, A. et al. A novel telomerase template antagonist (GRN163) as a potential anticancer agent. Cancer Res. 63, 3931-3939 (2003). 

  76. Oncogene B Herbert 24 5262 2005 10.1038/sj.onc.1208760 Herbert, B. et al. Lipid modification of GRN163, an N3′→P5′ thio-phosphoramidate oligonucleotide, enhances the potency of telomerase inhibition. Oncogene 24, 5262-5268 (2005). GRN163L, a telomerase inhibitor now in clinical trials, is demonstrated to have significantly enhanced cellular activity compared with its non-lipidated parent compound, GRN163. 

  77. Cancer Res. ZG Dikmen 65 1 2005 10.1158/0008-5472.CAN-05-1215 Dikmen, Z. G. et al. In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res. 65, 1-8 (2005). 

  78. Cancer Res. DA Jackson 67 1121 2007 10.1158/0008-5472.CAN-06-2306 Jackson, D. A. et al. Antiadhesive effects of GRN163L - an oligonucleotide N3′→P5′ thio-phosphoramidate targeting telomerase. Cancer Res. 67, 1121-1129 (2007). 

  79. 10.1007/s10549-005-9043-5 Gellert, G. C., Dikmen, Z. G., Wright, W. E., Gryaznov, S. & Shay, J. W. Effects of a novel telomerase inhibitor, GRN163L, in human breast cancer. Breast Cancer Res. Treat. 1-9 (2005). 

  80. Clin. Cancer Res. AE Hochreiter 12 3184 2006 10.1158/1078-0432.CCR-05-2760 Hochreiter, A. E. et al. Telomerase template antagonist GRN163L disrupts telomere maintenance, tumor growth, and metastasis of breast cancer. Clin. Cancer Res. 12, 3184-3192 (2006). 

  81. Int. J. Radiat. Oncol. Biol. Phys. J Gomez-Millan 67 897 2007 10.1016/j.ijrobp.2006.09.038 Gomez-Millan, J., Goldblatt, E. M., Gryaznov, S. M., Mendonca, M. S. & Herbert, B. S. Specific telomere dysfunction induced by GRN163L increases radiation sensitivity in breast cancer cells. Int. J. Radiat. Oncol. Biol. Phys. 67, 897-905 (2007). A representative report illustrating the telomere length-dependent activity of GRN163L in certain tumours, and synergy of telomerase inhibition and radiation in models of breast cancer. 

  82. Hepatology MW Djojosubroto 42 1 2005 10.1002/hep.20822 Djojosubroto, M. W. et al. Telomerase antagonists GRN163 and GRN163L inhibit tumor growth and increase chemosensitivity of human hepatoma. Hepatology 42, 1-12 (2005). 

  83. Neuro Oncol. T Ozawa 6 218 2004 10.1215/S1152851704000055 Ozawa, T. et al. Antitumor effects of specific telomerase inhibitor GRN163 in human glioblastoma xenografts. Neuro Oncol. 6, 218-226 (2004). 

  84. 10.1002/jcb.21635 Dikmen, Z. G., Wright, W. E., Shay, J. W. & Gryaznov, S. M. Telomerase targeted oligonucleotide thio-phosphoramidates in T24-luc bladder cancer cells. J. Cell Biochem. (2007). 

  85. Cancer Res. M Akiyama 63 6187 2003 Akiyama, M. et al. Effects of oligonucleotide N3′→P5′ thio-phosphoramidate (GRN163) targeting telomerase RNA in human multiple myeloma cells. Cancer Res. 63, 6187-6194 (2003). 

  86. Blood ES Wang 103 258 2004 10.1182/blood-2003-02-0546 Wang, E. S. et al. Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma. Blood 103, 258-266 (2004). 

  87. Nature Med. NK Nair 6 1011 2000 10.1038/79519 Nair, N. K. et al. Induction of cytotoxic T cells responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. Nature Med. 6, 1011-1013 (2000). 

  88. Cancer Res. R Vonderheide 61 8366 2001 Vonderheide, R. et al. Equivalent induction of telomerase-specific cytotoxic T lymphocytes from tumor-bearing patients and healthy individuals. Cancer Res. 61, 8366-8370 (2001). 

  89. Science SB Cohen 315 1850 2007 10.1126/science.1138596 Cohen, S. B. et al. Protein composition of catalytically active human telomerase from immortal cells. Science 315, 1850-1853 (2007). The first report of a substantially pure form of human telomerase and the essential protein components associated with telomerase activity in a cell-free system. 

  90. J. Immunol. M Gannage 174 8210 2005 10.4049/jimmunol.174.12.8210 Gannage, M. et al. Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients with chronic myeloid leukemia: implications for vaccine development and adoptive cellular immunotherapy. J. Immunol. 174, 8210-8218 (2005). 

  91. Blood G Filaci 107 1505 2005 10.1182/blood-2005-01-0258 Filaci, G. et al. Frequency of telomerase-specific CD8+ T lymphocytes in cancer patients. Blood 107, 1505-1512 (2005). 

  92. Curr. Opin. Mol. Ther. P Nava-Parada 9 490 2007 Nava-Parada, P. & Emens, L. A. GV-1001, an injectable telomerase peptide vaccine for the treatment of solid cancers. Curr. Opin. Mol. Ther. 9, 490-497 (2007). The immulogical and apparent clinical responses with GV1001, a telomerase peptide vaccine now in phase II and III studies, are reported. 

  93. Cancer Immunol. Immunother. PF Brunsvig 55 1553 2006 10.1007/s00262-006-0145-7 Brunsvig, P. F. et al. Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer. Cancer Immunol. Immunother. 55, 1553-1564 (2006). 

  94. Cancer Res. Z Su 62 5041 2002 Su, Z. et al. Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product. Cancer Res. 62, 5041-5048 (2002). 

  95. Cancer Research Z. Gunnur Dikmen 65 17 7866 2005 10.1158/0008-5472.CAN-05-1215 Dikmen, Z. et al. In vivo inhibition of lung cancer by GRN163L: a novel human telomerase inhibitor. Cancer Res. 7866-7873 (2005). 

  96. Clin. Cancer Res. RH Vonderheide 10 828 2004 10.1158/1078-0432.CCR-0620-3 Vonderheide, R. H. et al. Vaccination of cancer patients against telomerase induces functional antitumor CD8+ T lymphocytes. Clin. Cancer Res. 10, 828-839 (2004). 

  97. J. Immunol. Z Su 174 3798 2005 10.4049/jimmunol.174.6.3798 Su, Z. et al. Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J. Immunol. 174, 3798-3807 (2005). Strong immunological responses and signs of apparent clinical activity associated with immune responses are reported in prostate cancer patients given autologous TERT mRNA-transfected dendritic cell vaccines. 

  98. Oncology D Mavroudis 70 306 2006 10.1159/000096252 Mavroudis, D. et al. A phase I study of the optimized cryptic peptide TERT572Y in patients with advanced malignancies. Oncology 70, 306-314 (2006). 

  99. Clin. Cancer Res. MR Parkhurst 10 4688 2004 10.1158/1078-0432.CCR-04-0325 Parkhurst, M. R. et al. Immunization of patients with the hTERT:540-548 peptide induces peptide-reactive T lymphocytes that do not recognize tumors endogenously expressing telomerase. Clin. Cancer Res. 10, 4688-4698 (2004). 

  100. Res. SM Domchek 67 10546 2007 Domchek, S. M. et al. Telomerase-specific T-cell immunity in breast cancer: effect of vaccination on tumor immunosurveillance. Cancer Res. 67, 10546-10555 (2007). Induction of TERT-specific tumour-infiltrating cytotoxic T cells is associated with apparent signs of clinical activity with a TERT peptide vaccine, and patients with induced immune responses had longer median survival than those without induced immune responses. 

  101. J. Invest. Dermatol. RD Ramirez 108 113 1997 10.1111/1523-1747.ep12285654 Ramirez, R. D., Wright, W. E., Shay, J. W. & Taylor, R. S. Implications of telomerase activity in human hair follicles. J. Invest. Dermatol. 108, 113-117 (1997). 

  102. Exp. Hematol. GA Danet-Desnoyers 33 1275 2005 10.1016/j.exphem.2005.07.011 Danet-Desnoyers, G. A., Luongo, J. L., Bonnet, D. A., Domchek, S. M. & Vonderheide, R. H. Telomerase vaccination has no detectable effect on SCID-repopulating and colony-forming activities in the bone marrow of cancer patients. Exp. Hematol. 33, 1275-1280 (2005). 

  103. Br. J. Cancer M Hultdin 88 593 2003 10.1038/sj.bjc.6600763 Hultdin, M. et al. Association between telomere length and VH gene mutation status in chronic lymphocytic leukaemia: clinical and biological implications. Br. J. Cancer 88, 593-598 (2003). 

  104. Blood RN Damle 103 375 2004 10.1182/blood-2003-04-1345 Damle, R. N. et al. Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood 103, 375-382 (2004). 

  105. Proc. Natl Acad. Sci. USA CM Counter 91 2900 1994 10.1073/pnas.91.8.2900 Counter, C. M., Hirte, H. W., Bacchetti, S. & Harley, C. B. Telomerase activity in human ovarian carcinoma. Proc. Natl Acad. Sci. USA 91, 2900-2904 (1994). The first demonstration of specific telomerase expression in human tumour biopsy samples. 

  106. Cancer Gene Ther. G Saretzki 8 827 2001 10.1038/sj.cgt.7700383 Saretzki, G., Ludwig, A., von Zglinicki, T. & Runnebaum, I. Ribozyme-mediated telomerase inhibition induces immediate cell loss but not telomere shortening in ovarian cancer cells. Cancer Gene Ther. 8, 827-834 (2001). 

  107. J. Biol. Chem. F Jiang 279 53213 2004 10.1074/jbc.M410395200 Jiang, F., Bao, J., Li, P., Nicosia, S. V. & Bai, W. Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation. J. Biol. Chem. 279, 53213-53221 (2004). 

  108. Leukemia A Roth 21 2456 2007 10.1038/sj.leu.2404968 Roth, A. et al. Short telomeres and high telomerase activity in T-cell prolymphocytic leukemia. Leukemia 21, 2456-2462 (2007). 

  109. Nature Genet. K-K Wong 26 85 2000 10.1038/79232 Wong, K.-K. et al. Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation. Nature Genet. 26, 85-88 (2000). 

  110. Nature Rev. Immunol. PJ Tacken 7 790 2007 10.1038/nri2173 Tacken, P. J., de Vries, J. M., Torensma, R. & Figdor, C. G. Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nature Rev. Immunol. 7, 790-802 (2007). 

  111. Exp. Gerontol. RB Effros 42 416 2007 10.1016/j.exger.2006.11.005 Effros, R. B. Telomerase induction in T cells: A cure for aging and disease? Exp. Gerontol. 42, 416-420 (2007). 

  112. J. Virol. JJ Goronzy 75 12182 2001 10.1128/JVI.75.24.12182-12187.2001 Goronzy, J. J. et al. Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals. J. Virol. 75, 12182-12187 (2001). 

  113. Br. J. Haematol. M Ostergaard 125 590 2004 10.1111/j.1365-2141.2004.04952.x Ostergaard, M., Olesen, L. H., Hasle, H. & Hokland, K. E. WT1 gene expression: An excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukemia patients - results from a single centre study. Br. J. Haematol. 125, 590-600 (2004). 

  114. Blood A Roth 102 849 2003 10.1182/blood-2002-07-2015 Roth, A. et al. Telomerase levels control the lifespan of human T lymphocytes. Blood 102, 849-857 (2003). 

  115. Proc. Natl Acad. Sci. USA H Vaziri 91 9857 1994 10.1073/pnas.91.21.9857 Vaziri, H. et al. Evidence for a mitotic clock in human hematopoietic stem cells: Loss of telomeric DNA with age. Proc. Natl Acad. Sci. USA 91, 9857-9860 (1994). 

  116. Leukemia M Engelhardt 12 13 1998 10.1038/sj.leu.2400889 Engelhardt, M. et al. Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy. Leukemia 12, 13-24 (1998). 

  117. Leukemia I Ricca 19 644 2005 10.1038/sj.leu.2403652 Ricca, I. et al. Marked telomere shortening in mobilized peripheral blood progenitor cells (PBPC) following two tightly spaced high-dose chemotherapy courses with G-CSF. Leukemia 19, 644-651 (2005). 

  118. Blood I Thornley 99 2387 2002 10.1182/blood.V99.7.2387 Thornley, I. et al. Early hematopoietic reconstitution after clinical stem cell transplantation: evidence for stochastic stem cell behavior and limited acceleration in telomere loss. Blood 99, 2387-2396 (2002). 

  119. Leukemia S Franco 17 401 2003 10.1038/sj.leu.2402815 Franco, S. et al. Telomere dynamics in childhood leukemia and solid tumors: a follow-up study. Leukemia 17, 401-410 (2003). 

  120. Curr. Mol. Med. CB Harley 5 205 2005 10.2174/1566524053586671 Harley, C. B. Telomerase therapeutics for degenerative diseases. Curr. Mol. Med. 5, 205-211 (2005). 

  121. J. Biol. Chem. ZH Zhong 282 29314 2007 10.1074/jbc.M701413200 Zhong, Z. H. et al. Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. J. Biol. Chem. 282, 29314-29322 (2007). 

  122. Genes Dev. S Chang 17 88 2003 10.1101/gad.1029903 Chang, S., Khoo, C. M., Naylor, M. L., Maser, R. S. & DePinho, R. A. Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression. Genes Dev. 17, 88-100 (2003). 

  123. Aging Cell B Unryn 4 97 2005 10.1111/j.1474-9728.2005.00144.x Unryn, B., Cook, L. & Riabowol, K. Paternal age is positively linked to telomere length of children. Aging Cell 4, 97-101 (2005). 

  124. Proc. Natl Acad. Sci. USA OT Njajou 104 12135 2007 10.1073/pnas.0702703104 Njajou, O. T. et al. Telomere length is paternally inherited and is associated with parental lifespan. Proc. Natl Acad. Sci. USA 104, 12135-12139 (2007). 

  125. Mol. Hum. Reprod. GA Ulaner 3 769 1997 10.1093/molehr/3.9.769 Ulaner, G. A. & Giudice, L. C. Developmental regulation of telomerase activity in human fetal tissues during gestation. Mol. Hum. Reprod. 3, 769-773 (1997). 

  126. Biol. Reprod. J Xu 63 1124 2000 10.1095/biolreprod63.4.1124 Xu, J. & Yang, X. Telomerase activity in bovine embryos during early development. Biol. Reprod. 63, 1124-1128 (2000). 

  127. Proc. Natl Acad. Sci. USA S Schaetzlein 101 8034 2004 10.1073/pnas.0402400101 Schaetzlein, S. et al. Telomere length is reset during early mammalian embryogenesis. Proc. Natl Acad. Sci. USA 101, 8034-8038 (2004). 

  128. Nature D Adda di Fagagna 426 194 2003 10.1038/nature02118 d' Adda di Fagagna, D. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194-198 (2003). 

  129. Science J Karlseder 295 2446 2002 10.1126/science.1069523 Karlseder, J., Smogorzewska, A. & de Lange, T. Senescence induced by altered telomere state, not telomere loss. Science 295, 2446-2449 (2002). 

  130. J. Mol. Biol. MZ Levy 225 951 1992 10.1016/0022-2836(92)90096-3 Levy, M. Z., Allsopp, R. C., Futcher, A. B., Greider, C. W. & Harley, C. B. Telomere end-replication problem and cell aging. J. Mol. Biol. 225, 951-960 (1992). 

  131. Nature Protoc. GM Baerlocher 1 2365 2006 10.1038/nprot.2006.263 Baerlocher, G. M., Vulto, I., de Jong, G. & Lansdorp, P. M. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nature Protoc. 1, 2365-2376 (2006). 

  132. Nature B van Steensel 385 740 1997 10.1038/385740a0 van Steensel, B. & de Lange, T. Control of telomere length by the human telomeric protein TRF1. Nature 385, 740-743 (1997). 

  133. Cell MT Teixeira 117 323 2004 10.1016/S0092-8674(04)00334-4 Teixeira, M. T., Arneric, M., Sperisen, P. & Lingner, J. Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell 117, 323-335 (2004). 

  134. J. Biol. Chem. M Ouellette 275 10072 2000 10.1074/jbc.275.14.10072 Ouellette, M. et al. Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase. J. Biol. Chem. 275, 10072-10076 (2000). 

  135. Proc. Natl Acad. Sci. USA Y Liu 99 3597 2002 10.1073/pnas.062549199 Liu, Y., Kha, H., Ungrin, M., Robinson, M. O. & Harrington, L. Preferential maintenance of critically short telomeres in mammalian cells heterozygous for mTert. Proc. Natl Acad. Sci. USA 99, 3597-3602 (2002). 

  136. Chromosoma N Hug 115 413 2006 10.1007/s00412-006-0067-3 Hug, N. & Lingner, J. Telomere length homeostasis. Chromosoma 115, 413-425 (2006). 

  137. Biochemistry G Wallweber 42 589 2003 10.1021/bi026914a Wallweber, G., Gryaznov, S., Pongracz, K. & Pruzan, R. Interaction of human telomerase with its primer substrate. Biochemistry 42, 589-600 (2003). Analysis of human telomerase primer binding and dissociation kinetics enabled characterization of the mechanism of action of template antagonist telomerase inhibitor GRN163L. 

  138. Cell M Hemann 107 67 2001 10.1016/S0092-8674(01)00504-9 Hemann, M., Strong, M., Hao, L. & Greider, C. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107, 67-77 (2001). 

  139. Biochimie DM Baird 90 116 2008 10.1016/j.biochi.2007.08.003 Baird, D. M. Telomere dynamics in human cells. Biochimie 90, 116-121 (2008). 

  140. Mol. Cell. Biol. JR Mitchell 19 567 1999 10.1128/MCB.19.1.567 Mitchell, J. R., Cheng, J. & Collins, K. A box H/ACA small nucleolar RNA-like domain at the human telomerase RNA 3′ end. Mol. Cell. Biol. 19, 567-576 (1999). 

  141. Br. J. Cancer SL Bernhardt 95 1474 2006 10.1038/sj.bjc.6603437 Bernhardt, S. L. et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study. Br. J. Cancer 95, 1474-1482 (2006). 

  142. J. Clin. Oncol. I Bolonaki 25 2727 2007 10.1200/JCO.2006.10.3465 Bolonaki, I. et al. Vaccination of patients with advanced non-small-cell lung cancer with an optimized cryptic human telomerase reverse transcriptase peptide. J. Clin. Oncol. 25, 2727-2734 (2007). 

  143. J. Clin. Oncol. FE Millard 22 2459 2004 10.1200/jco.2004.22.14_suppl.2519 Millard, F. E., Gerloni, M., Derrah, D., Farness, P. & Zanetti, M. Phase I study of transgenic B lymphocyte immunization (TLI) against telomerase in androgen-independent prostate cancer (PC). J. Clin. Oncol. 22, 2459 (2004). 

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