Treating Cancer by Targeting Telomeres and Telomerase
Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a cat...
Saved in:
Published in | Antioxidants Vol. 6; no. 1; p. 15 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
19.02.2017
MDPI |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells. While hTR is constitutively expressed in most tissue types, hTERT expression levels are low enough that telomere length cannot be maintained, which sets a proliferative lifespan on normal cells. However, in the majority of cancers, telomerase maintains stable telomere length, thereby conferring cell immortality. Levels of hTERT mRNA are directly related to telomerase activity, thereby making it a more suitable therapeutic target than hTR. Recent data suggests that stabilization of telomeric G-quadruplexes may act to indirectly inhibit telomerase action by blocking hTR binding. Telomeric DNA has the propensity to spontaneously form intramolecular G-quadruplexes, four-stranded DNA secondary structures that are stabilized by the stacking of guanine residues in a planar arrangement. The functional roles of telomeric G-quadruplexes are not completely understood, but recent evidence suggests that they can stall the replication fork during DNA synthesis and inhibit telomere replication by preventing telomerase and related proteins from binding to the telomere. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3' end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. However, inhibition of telomerase, either directly or indirectly, has shown only moderate success in cancer patients. Another promising approach of targeting the telomere is the use of guanine-rich oligonucleotides (GROs) homologous to the 3' telomere overhang sequence (T-oligos). T-oligos, particularly a specific 11-base oligonucleotide (5'-dGTTAGGGTTAG-3') called T11, have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell types with minimal or no cytostatic effects in normal, non-transformed cells. As a result, T-oligos and other GROs are being investigated as prospective anticancer therapeutics. Interestingly, the DDRs induced by T-oligos in cancer cells are similar to the effects seen after progressive telomere degradation in normal cells. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review, we discuss the current understanding of how T-oligos exert their antiproliferative effects in cancer cells and their role in inhibition of telomerase. We also discuss the current understanding of telomerase in cancer and various therapeutic targets related to the telomeres and telomerase. |
---|---|
AbstractList | Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells. While hTR is constitutively expressed in most tissue types, hTERT expression levels are low enough that telomere length cannot be maintained, which sets a proliferative lifespan on normal cells. However, in the majority of cancers, telomerase maintains stable telomere length, thereby conferring cell immortality. Levels of hTERT mRNA are directly related to telomerase activity, thereby making it a more suitable therapeutic target than hTR. Recent data suggests that stabilization of telomeric G-quadruplexes may act to indirectly inhibit telomerase action by blocking hTR binding. Telomeric DNA has the propensity to spontaneously form intramolecular G-quadruplexes, four-stranded DNA secondary structures that are stabilized by the stacking of guanine residues in a planar arrangement. The functional roles of telomeric G-quadruplexes are not completely understood, but recent evidence suggests that they can stall the replication fork during DNA synthesis and inhibit telomere replication by preventing telomerase and related proteins from binding to the telomere. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3' end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. However, inhibition of telomerase, either directly or indirectly, has shown only moderate success in cancer patients. Another promising approach of targeting the telomere is the use of guanine-rich oligonucleotides (GROs) homologous to the 3' telomere overhang sequence (T-oligos). T-oligos, particularly a specific 11-base oligonucleotide (5'-dGTTAGGGTTAG-3') called T11, have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell types with minimal or no cytostatic effects in normal, non-transformed cells. As a result, T-oligos and other GROs are being investigated as prospective anticancer therapeutics. Interestingly, the DDRs induced by T-oligos in cancer cells are similar to the effects seen after progressive telomere degradation in normal cells. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review, we discuss the current understanding of how T-oligos exert their antiproliferative effects in cancer cells and their role in inhibition of telomerase. We also discuss the current understanding of telomerase in cancer and various therapeutic targets related to the telomeres and telomerase. |
Author | Leviskas, Brandon Puri, Neelu Wojdyla, Luke Sanjali, Ankita Kuckovic, Adijan Schrank, Zachary Ivancich, Marko |
AuthorAffiliation | Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA; msi4@students.calvin.edu (M.I.); zacharyschrank15@augustana.edu (Z.S.); lukewojdyla@gmail.com (L.W.); brandonleviskas@gmail.com (B.L.); ak147356@rockford.edu (A.K.); ankita.sanjaali@gmail.com (A.S.) |
AuthorAffiliation_xml | – name: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA; msi4@students.calvin.edu (M.I.); zacharyschrank15@augustana.edu (Z.S.); lukewojdyla@gmail.com (L.W.); brandonleviskas@gmail.com (B.L.); ak147356@rockford.edu (A.K.); ankita.sanjaali@gmail.com (A.S.) |
Author_xml | – sequence: 1 givenname: Marko surname: Ivancich fullname: Ivancich, Marko email: msi4@students.calvin.edu organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. msi4@students.calvin.edu – sequence: 2 givenname: Zachary surname: Schrank fullname: Schrank, Zachary email: zacharyschrank15@augustana.edu organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. zacharyschrank15@augustana.edu – sequence: 3 givenname: Luke surname: Wojdyla fullname: Wojdyla, Luke email: lukewojdyla@gmail.com organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. lukewojdyla@gmail.com – sequence: 4 givenname: Brandon surname: Leviskas fullname: Leviskas, Brandon email: brandonleviskas@gmail.com organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. brandonleviskas@gmail.com – sequence: 5 givenname: Adijan surname: Kuckovic fullname: Kuckovic, Adijan email: ak147356@rockford.edu organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. ak147356@rockford.edu – sequence: 6 givenname: Ankita surname: Sanjali fullname: Sanjali, Ankita email: ankita.sanjaali@gmail.com organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. ankita.sanjaali@gmail.com – sequence: 7 givenname: Neelu surname: Puri fullname: Puri, Neelu email: neelupur@uic.edu organization: Department of Biomedical Sciences, College of Medicine at Rockford, University of Illinois, Rockford, IL 61107, USA. neelupur@uic.edu |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28218725$$D View this record in MEDLINE/PubMed |
BookMark | eNpdkc9vFCEUx4mpsT_s0avZxIuXUR4MA1xMzEZrkyZe1jN5MI91NrNQYda0_72z3bbpygV475NP4H3P2UnKiRh7B_yTlJZ_xjQN-a7jwDmoV-xMcN010go4eXE-ZZe1bvi8LEjD7Rt2KowAo4U6Y2pVCKchrRdLTIHKwt8vVljW9FBb0Zi3VKguMPVPN6z0lr2OOFa6fNwv2K_v31bLH83Nz6vr5debJqhWT40QEMCQ7FH2YKNHEQ1oy70xUYouIoq5oZUWkoLvZcQAqGxUIXhCtPKCXR-8fcaNuy3DFsu9yzi4h0Iua4dlGsJIjrpWI4fOR-VbYVujPLYtcBu5hi6Y2fXl4Lrd-S31gdJUcDySHnfS8Nut81-npGlB7wUfHwUl_9lRndx2qIHGERPlXXXzRHnXSpDdjH74D93kXUnzqGbKGGuFNHuqOVCh5FoLxefHAHf7fN1RvjP__uUPnumnNOU_plOisg |
CitedBy_id | crossref_primary_10_1093_jnci_djac226 crossref_primary_10_1021_acs_jmedchem_2c01668 crossref_primary_10_3390_ijms232112844 crossref_primary_10_1016_j_antiviral_2019_104695 crossref_primary_10_3390_ijms19010013 crossref_primary_10_3390_cells13110884 crossref_primary_10_1016_j_jaut_2021_102699 crossref_primary_10_3390_genes9050241 crossref_primary_10_3390_ijms20081823 crossref_primary_10_1016_j_bbrep_2021_100937 crossref_primary_10_1038_s41598_021_82917_7 crossref_primary_10_3233_TUB_211515 crossref_primary_10_1002_cbf_3398 crossref_primary_10_1016_j_biopha_2018_01_004 crossref_primary_10_1016_j_omtn_2022_11_008 crossref_primary_10_1002_ardp_202000450 crossref_primary_10_1080_07391102_2023_2292793 crossref_primary_10_3390_cancers12082260 crossref_primary_10_1186_s12885_018_4633_x crossref_primary_10_1155_2018_7184253 crossref_primary_10_3390_sym12081214 crossref_primary_10_3390_molecules24030396 crossref_primary_10_1093_mtomcs_mfab029 crossref_primary_10_1038_s41598_018_24503_y crossref_primary_10_3389_fimmu_2020_589929 crossref_primary_10_3389_fonc_2019_00344 crossref_primary_10_1016_j_yexmp_2019_104354 crossref_primary_10_1016_j_jid_2019_06_149 crossref_primary_10_1016_j_microc_2023_108776 crossref_primary_10_3390_cancers12030558 crossref_primary_10_1016_j_biochi_2020_11_015 crossref_primary_10_1002_iub_2460 crossref_primary_10_1007_s00018_019_03261_8 crossref_primary_10_3390_cells11162482 crossref_primary_10_1016_j_drudis_2019_05_015 crossref_primary_10_1016_j_lfs_2020_117398 crossref_primary_10_1007_s10549_018_4850_7 crossref_primary_10_3390_cancers14071655 crossref_primary_10_1039_C9OB02111F crossref_primary_10_2174_1568026620666200109114339 crossref_primary_10_3390_ijms20133186 crossref_primary_10_1016_j_bmcl_2017_08_044 crossref_primary_10_3390_ph17010030 crossref_primary_10_1016_j_ejmech_2023_115121 crossref_primary_10_1186_s12885_024_12379_3 crossref_primary_10_1080_15257770_2023_2188220 crossref_primary_10_3390_genes12101632 crossref_primary_10_1016_j_bios_2018_08_069 crossref_primary_10_3390_cancers12092337 crossref_primary_10_1021_acsomega_8b01574 crossref_primary_10_4037_aacnacc2018378 crossref_primary_10_3390_fermentation8100473 crossref_primary_10_1016_j_molstruc_2018_03_034 crossref_primary_10_4103_glioma_glioma_20_20 crossref_primary_10_1016_j_aca_2018_04_071 crossref_primary_10_1002_prp2_882 crossref_primary_10_3390_molecules23092267 |
Cites_doi | 10.1158/1078-0432.CCR-05-2760 10.2174/1871520615666150202100130 10.3892/ol.2011.354 10.1016/j.canlet.2013.09.010 10.18632/aging.100210 10.1158/0008-5472.CAN-04-2910 10.3390/genes7060022 10.1016/j.tibs.2013.07.001 10.1007/s10815-015-0574-3 10.1007/s13277-015-3575-z 10.1016/j.yexmp.2009.01.004 10.1093/hmg/6.1.69 10.1007/s10549-005-9043-5 10.3390/genes8020055 10.1038/nrd3868 10.1186/bcr1646 10.1038/ncb3240 10.1111/j.1474-9726.2011.00718.x 10.1007/s13346-013-0161-z 10.1038/sj.onc.1209577 10.1038/sj.onc.1209217 10.1172/JCI79134 10.1158/0008-5472.CAN-10-1588 10.3390/genes7060029 10.1073/pnas.0235444100 10.1158/0008-5472.CAN-13-3568 10.1038/sj.onc.1202898 10.1016/S0092-8674(00)80932-0 10.1016/j.cancergen.2013.10.001 10.1172/JCI32461 10.1101/gad.271783.115 10.18632/oncotarget.11093 10.1038/ncomms1209 10.1111/and.12008 10.1016/j.febslet.2004.11.036 10.1039/c3bm00006k 10.1182/blood-2007-09-111245 10.1128/MCB.01352-08 10.1096/fj.02-0197com 10.1016/j.febslet.2010.05.026 10.1002/ijc.23946 10.1007/s00412-015-0555-4 10.1158/0008-5472.CAN-11-3336 10.1089/oli.2009.0179 10.1089/nat.2013.0420 10.1155/2015/546210 10.1089/nat.2012.0401 10.1006/excr.1999.4613 10.1038/sj.onc.1205080 10.2174/1381612820666140630100702 10.1016/j.addr.2003.12.002 10.1172/JCI86042 10.1111/j.1349-7006.2008.00878.x 10.1186/bcr2639 10.1128/MCB.00476-09 10.1158/2159-8290.CD-16-0177 10.1016/j.bcp.2007.06.011 10.18632/oncotarget.1047 10.1073/pnas.0503095102 10.1038/nature08137 10.1016/j.bbrc.2014.03.013 10.1155/2010/928628 10.1016/j.ctrv.2012.06.007 10.3389/fonc.2012.00180 10.1073/pnas.96.25.14276 10.1124/mol.105.013300 10.1097/CAD.0b013e3282f5d4c2 10.1126/science.1069523 10.1038/82586 10.1038/nrm2848 10.1016/S0888-7543(02)00033-2 10.18632/oncotarget.10634 10.1053/j.seminhematol.2013.03.030 10.1093/annonc/mdu550 10.1038/13495 10.1128/MCB.22.1.332-342.2002 10.1096/fj.04-1774com 10.1186/s13073-016-0324-x 10.1073/pnas.0607332103 10.1016/j.ccr.2004.11.021 10.1016/j.celrep.2013.08.040 10.1038/sj.onc.1205083 10.1038/nrg2763 |
ContentType | Journal Article |
Copyright | Copyright MDPI AG 2017 2017 by the authors. 2017 |
Copyright_xml | – notice: Copyright MDPI AG 2017 – notice: 2017 by the authors. 2017 |
DBID | NPM AAYXX CITATION 7QR 7T5 7TO 8FD 8FE 8FH ABUWG AFKRA AZQEC BBNVY BENPR BHPHI CCPQU DWQXO FR3 GNUQQ H94 HCIFZ LK8 M7P P64 PIMPY PQEST PQQKQ PQUKI PRINS 7X8 5PM DOA |
DOI | 10.3390/antiox6010015 |
DatabaseName | PubMed CrossRef Chemoreception Abstracts Immunology Abstracts Oncogenes and Growth Factors Abstracts Technology Research Database ProQuest SciTech Collection ProQuest Natural Science Collection ProQuest Central (Alumni) ProQuest Central ProQuest Central Essentials Biological Science Collection ProQuest Central Natural Science Collection ProQuest One Community College ProQuest Central Engineering Research Database ProQuest Central Student AIDS and Cancer Research Abstracts SciTech Premium Collection Biological Sciences Biological Science Database Biotechnology and BioEngineering Abstracts Publicly Available Content Database ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China MEDLINE - Academic PubMed Central (Full Participant titles) DOAJ Directory of Open Access Journals |
DatabaseTitle | PubMed CrossRef Publicly Available Content Database ProQuest Central Student Oncogenes and Growth Factors Abstracts Technology Research Database ProQuest Central Essentials ProQuest Central (Alumni Edition) SciTech Premium Collection ProQuest One Community College ProQuest Natural Science Collection ProQuest Central China ProQuest Central Natural Science Collection ProQuest Central Korea Biological Science Collection AIDS and Cancer Research Abstracts Chemoreception Abstracts ProQuest Biological Science Collection ProQuest One Academic Eastern Edition Biological Science Database ProQuest SciTech Collection Biotechnology and BioEngineering Abstracts ProQuest One Academic UKI Edition Immunology Abstracts Engineering Research Database ProQuest One Academic MEDLINE - Academic |
DatabaseTitleList | PubMed Publicly Available Content Database |
Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Engineering |
EISSN | 2076-3921 |
ExternalDocumentID | oai_doaj_org_article_e647a016bf5b429485ba44109f0716c8 10_3390_antiox6010015 28218725 |
Genre | Journal Article Review |
GroupedDBID | 53G 5VS 8FE 8FH AADQD AAFWJ AAHBH ADBBV ADRAZ AFKRA AFPKN AFZYC ALMA_UNASSIGNED_HOLDINGS AOIJS BBNVY BCNDV BENPR BHPHI CCPQU GROUPED_DOAJ HCIFZ HYE KQ8 LK8 M48 M7P MODMG M~E NPM OK1 PIMPY PROAC RPM AAYXX CITATION PGMZT 7QR 7T5 7TO 8FD ABUWG AZQEC DWQXO FR3 GNUQQ H94 P64 PQEST PQQKQ PQUKI PRINS 7X8 5PM |
ID | FETCH-LOGICAL-c547t-221c18e3da3d19fba2f81790b88f326faa23d175723ecbd3fac1a59f5ccbeaa93 |
IEDL.DBID | RPM |
ISSN | 2076-3921 |
IngestDate | Thu Jul 04 21:08:42 EDT 2024 Tue Sep 17 21:18:09 EDT 2024 Fri Aug 16 07:47:00 EDT 2024 Fri Sep 13 07:49:47 EDT 2024 Fri Aug 23 03:04:37 EDT 2024 Sun Jun 23 00:36:21 EDT 2024 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 1 |
Keywords | telomere homolog oligonucleotides (T-oligos) shelterin complex guanine-rich oligonucleotides (GROs) telomerase DNA damage responses G-quadruplex |
Language | English |
License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c547t-221c18e3da3d19fba2f81790b88f326faa23d175723ecbd3fac1a59f5ccbeaa93 |
Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384178/ |
PMID | 28218725 |
PQID | 1888992386 |
PQPubID | 2032435 |
ParticipantIDs | doaj_primary_oai_doaj_org_article_e647a016bf5b429485ba44109f0716c8 pubmedcentral_primary_oai_pubmedcentral_nih_gov_5384178 proquest_miscellaneous_1870643136 proquest_journals_1888992386 crossref_primary_10_3390_antiox6010015 pubmed_primary_28218725 |
PublicationCentury | 2000 |
PublicationDate | 20170219 |
PublicationDateYYYYMMDD | 2017-02-19 |
PublicationDate_xml | – month: 2 year: 2017 text: 20170219 day: 19 |
PublicationDecade | 2010 |
PublicationPlace | Switzerland |
PublicationPlace_xml | – name: Switzerland – name: Basel |
PublicationTitle | Antioxidants |
PublicationTitleAlternate | Antioxidants (Basel) |
PublicationYear | 2017 |
Publisher | MDPI AG MDPI |
Publisher_xml | – name: MDPI AG – name: MDPI |
References | 23997932 - Biomater Sci. 2013 Jul;1(7):719-727 27509060 - Oncotarget. 2016 Aug 30;7(35):55939-55950 11850778 - Oncogene. 2002 Jan 21;21(4):532-40 11101843 - Nat Genet. 2000 Dec;26(4):447-50 25467017 - Ann Oncol. 2015 Feb;26(2):354-62 15680963 - FEBS Lett. 2005 Feb 7;579(4):859-62 16302000 - Oncogene. 2006 Mar 23;25(13):1955-66 10502820 - Nat Med. 1999 Oct;5(10):1164-70 20652008 - J Oncol. 2010;2010:928628 20125188 - Nat Rev Mol Cell Biol. 2010 Mar;11(3):171-81 22440753 - Cancer Res. 2012 Jun 1;72(11):2822-32 15333580 - FASEB J. 2004 Sep;18(12):1373-81 20351727 - Nat Rev Genet. 2010 May;11(5):319-30 21343924 - Nat Commun. 2011 Feb 22;2:206 21037379 - Aging (Albany NY). 2010 Oct;2(10 ):691-708 28146113 - Genes (Basel). 2017 Jan 31;8(2):null 26022158 - Tumour Biol. 2015 Nov;36(11):8425-37 19003960 - Int J Cancer. 2009 Jan 15;124(2):473-82 25893605 - J Clin Invest. 2015 May;125(5):2109-22 21518243 - Aging Cell. 2011 Oct;10(5):761-8 22866138 - Oncol Lett. 2011 Sep 1;2(5):845-850 12515865 - Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):527-31 11923537 - Science. 2002 Mar 29;295(5564):2446-9 24391441 - Int J Nanomedicine. 2014;9:43-53 19571879 - Nature. 2009 Jul 2;460(7251):66-72 10502398 - Exp Cell Res. 1999 Oct 10;252(1):41-9 15652747 - Cancer Cell. 2005 Jan;7(1):25-37 11739745 - Mol Cell Biol. 2002 Jan;22(1):332-42 23956466 - Semin Hematol. 2013 Apr;50(2):165-74 23634944 - Nucleic Acid Ther. 2013 Jun;23(3):167-74 16652154 - Oncogene. 2006 Sep 21;25(42):5719-25 27240403 - Genes (Basel). 2016 May 26;7(6):null 25786618 - Drug Deliv Transl Res. 2014 Feb;4(1):74-83 20493857 - FEBS Lett. 2010 Sep 10;584(17):3819-25 24041868 - Cancer Lett. 2014 Feb 1;343(1):14-23 26525972 - Chromosoma. 2016 Jun;125(2):337-51 18454043 - Anticancer Drugs. 2008 Apr;19(4):329-38 24599132 - Cancer Res. 2014 Mar 15;74(6):1639-44 23197039 - Nat Rev Drug Discov. 2012 Dec;11(12):923-36 26584619 - Genes Dev. 2015 Dec 1;29(23):2420-34 17631279 - Biochem Pharmacol. 2007 Sep 1;74(5):679-89 27323951 - Genome Med. 2016 Jun 20;8(1):69 26389665 - Nat Cell Biol. 2015 Oct;17(10):1327-38 11850781 - Oncogene. 2002 Jan 21;21(4):564-79 24095731 - Cell Rep. 2013 Oct 17;5(1):194-206 26783410 - Evid Based Complement Alternat Med. 2015;2015:546210 23226680 - Front Oncol. 2012 Nov 30;2:180 17257427 - Breast Cancer Res. 2007;9(1):R13 24632202 - Biochem Biophys Res Commun. 2014 Apr 4;446(2):596-601 9476899 - Cell. 1998 Feb 6;92(3):401-13 19454272 - Exp Mol Pathol. 2009 Jun;86(3):151-64 16319992 - Breast Cancer Res Treat. 2006 Mar;96(1):73-81 24331919 - Cancer Genet. 2013 Nov;206(11):374-86 17015833 - Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15073-8 27650951 - Cancer Discov. 2016 Nov;6(11):1276-1291 27322328 - Genes (Basel). 2016 Jun 17;7(6):null 26411311 - J Assist Reprod Genet. 2015 Nov;32(11):1685-90 18955498 - Mol Cell Biol. 2009 Jan;29(2):471-82 15109768 - Adv Drug Deliv Rev. 2004 May 7;56(9):1257-72 15735037 - Cancer Res. 2005 Feb 15;65(4):1489-96 25642982 - Anticancer Agents Med Chem. 2015;15(7):856-68 24975605 - Curr Pharm Des. 2014;20(41):6422-37 20846433 - Breast Cancer Res. 2010;12(5):R71 27449293 - Oncotarget. 2016 Aug 16;7(33):53127-53136 19667071 - Mol Cell Biol. 2009 Oct;29(20):5552-63 22841437 - Cancer Treat Rev. 2013 Aug;39(5):444-56 16150933 - Mol Pharmacol. 2005 Dec;68(6):1551-8 21071633 - Cancer Res. 2011 Jan 1;71(1):266-76 10498864 - Oncogene. 1999 Sep 16;18(37):5148-58 12873987 - Cancer Res. 2003 Jul 15;63(14):3931-9 23971906 - Nucleic Acid Ther. 2013 Oct;23(5):311-21 16707619 - Clin Cancer Res. 2006 May 15;12(10):3184-92 27643433 - J Clin Invest. 2016 Oct 3;126(10 ):4045-4060 12554694 - FASEB J. 2003 Feb;17(2):152-62 19642913 - Oligonucleotides. 2009 Sep;19(3):287-92 23932019 - Trends Biochem Sci. 2013 Sep;38(9):426-34 12676566 - Genomics. 2003 Apr;81(4):422-32 9002672 - Hum Mol Genet. 1997 Jan;6(1):69-76 22928904 - Andrologia. 2013 Oct;45(5):289-304 17932567 - J Clin Invest. 2007 Nov;117(11):3236-47 10588696 - Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14276-81 18754863 - Cancer Sci. 2008 Aug;99(8):1528-38 15928077 - Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8222-7 23800953 - Oncotarget. 2013 May;4(5):761-71 18077792 - Blood. 2008 Feb 15;111(4):2388-91 ref13 ref57 ref12 ref56 ref15 ref59 ref14 ref58 ref53 ref52 ref55 ref10 ref54 ref17 ref16 ref19 ref18 Uppada (ref66) 2014; 9 ref51 ref50 ref46 ref45 Hahn (ref47) 1999; 5 ref48 ref42 ref41 ref85 ref44 ref43 ref49 Asai (ref22) 2003; 63 ref8 ref7 ref9 ref4 ref3 ref6 ref5 ref82 ref81 ref40 ref84 ref83 ref80 ref35 ref79 ref34 ref78 ref36 ref31 ref75 ref30 ref74 ref33 ref77 ref32 ref76 ref2 ref1 ref39 ref38 Cookson (ref37) 2005; 68 Dunham (ref11) 2000; 26 ref71 ref70 ref73 ref72 ref24 ref68 ref23 ref67 ref26 ref25 ref69 ref20 ref64 ref63 ref21 ref65 ref28 ref27 ref29 ref60 ref62 ref61 |
References_xml | – ident: ref24 doi: 10.1158/1078-0432.CCR-05-2760 – ident: ref85 doi: 10.2174/1871520615666150202100130 – ident: ref18 doi: 10.3892/ol.2011.354 – ident: ref64 doi: 10.1016/j.canlet.2013.09.010 – ident: ref30 doi: 10.18632/aging.100210 – ident: ref35 doi: 10.1158/0008-5472.CAN-04-2910 – ident: ref13 doi: 10.3390/genes7060022 – ident: ref41 doi: 10.1016/j.tibs.2013.07.001 – ident: ref5 doi: 10.1007/s10815-015-0574-3 – ident: ref32 doi: 10.1007/s13277-015-3575-z – ident: ref58 doi: 10.1016/j.yexmp.2009.01.004 – ident: ref77 doi: 10.1093/hmg/6.1.69 – ident: ref23 doi: 10.1007/s10549-005-9043-5 – ident: ref34 doi: 10.3390/genes8020055 – ident: ref28 doi: 10.1038/nrd3868 – ident: ref67 doi: 10.1186/bcr1646 – ident: ref48 doi: 10.1038/ncb3240 – ident: ref75 doi: 10.1111/j.1474-9726.2011.00718.x – ident: ref83 doi: 10.1007/s13346-013-0161-z – ident: ref33 doi: 10.1038/sj.onc.1209577 – ident: ref39 doi: 10.1038/sj.onc.1209217 – ident: ref45 doi: 10.1172/JCI79134 – ident: ref42 doi: 10.1158/0008-5472.CAN-10-1588 – ident: ref14 doi: 10.3390/genes7060029 – ident: ref54 doi: 10.1073/pnas.0235444100 – ident: ref40 doi: 10.1158/0008-5472.CAN-13-3568 – ident: ref55 doi: 10.1038/sj.onc.1202898 – ident: ref70 doi: 10.1016/S0092-8674(00)80932-0 – ident: ref52 doi: 10.1016/j.cancergen.2013.10.001 – ident: ref38 doi: 10.1172/JCI32461 – ident: ref15 doi: 10.1101/gad.271783.115 – ident: ref26 doi: 10.18632/oncotarget.11093 – ident: ref81 doi: 10.1038/ncomms1209 – ident: ref3 doi: 10.1111/and.12008 – ident: ref50 doi: 10.1016/j.febslet.2004.11.036 – ident: ref82 doi: 10.1039/c3bm00006k – ident: ref19 doi: 10.1182/blood-2007-09-111245 – ident: ref78 doi: 10.1128/MCB.01352-08 – ident: ref72 doi: 10.1096/fj.02-0197com – ident: ref17 doi: 10.1016/j.febslet.2010.05.026 – ident: ref60 doi: 10.1002/ijc.23946 – ident: ref4 doi: 10.1007/s00412-015-0555-4 – ident: ref29 doi: 10.1158/0008-5472.CAN-11-3336 – ident: ref56 doi: 10.1089/oli.2009.0179 – ident: ref57 doi: 10.1089/nat.2013.0420 – ident: ref79 doi: 10.1155/2015/546210 – ident: ref62 doi: 10.1089/nat.2012.0401 – ident: ref73 doi: 10.1006/excr.1999.4613 – ident: ref7 doi: 10.1038/sj.onc.1205080 – ident: ref1 doi: 10.2174/1381612820666140630100702 – ident: ref84 doi: 10.1016/j.addr.2003.12.002 – ident: ref46 doi: 10.1172/JCI86042 – ident: ref53 doi: 10.1111/j.1349-7006.2008.00878.x – ident: ref59 doi: 10.1186/bcr2639 – ident: ref8 doi: 10.1128/MCB.00476-09 – ident: ref49 doi: 10.1158/2159-8290.CD-16-0177 – ident: ref36 doi: 10.1016/j.bcp.2007.06.011 – ident: ref71 doi: 10.18632/oncotarget.1047 – ident: ref43 doi: 10.1073/pnas.0503095102 – ident: ref44 doi: 10.1038/nature08137 – ident: ref61 doi: 10.1016/j.bbrc.2014.03.013 – ident: ref65 doi: 10.1155/2010/928628 – ident: ref2 doi: 10.1016/j.ctrv.2012.06.007 – ident: ref12 doi: 10.3389/fonc.2012.00180 – ident: ref25 doi: 10.1073/pnas.96.25.14276 – volume: 68 start-page: 1551 year: 2005 ident: ref37 article-title: Pharmacodynamics of the G-quadruplex-stabilizing telomerase inhibitor 3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate (RHPS4) in vitro: Activity in human tumor cells correlates with telomere length and can be enhanced, or antagonized, with cytotoxic agents publication-title: Mol. Pharmacol. doi: 10.1124/mol.105.013300 contributor: fullname: Cookson – ident: ref68 doi: 10.1097/CAD.0b013e3282f5d4c2 – volume: 63 start-page: 3931 year: 2003 ident: ref22 article-title: A novel telomerase template antagonist (GRN163) as a potential anticancer agent publication-title: Cancer Res. contributor: fullname: Asai – ident: ref69 doi: 10.1126/science.1069523 – volume: 26 start-page: 447 year: 2000 ident: ref11 article-title: Telomere maintenance by recombination in human cells publication-title: Nat. Genet. doi: 10.1038/82586 contributor: fullname: Dunham – ident: ref6 doi: 10.1038/nrm2848 – volume: 9 start-page: 43 year: 2014 ident: ref66 article-title: Novel delivery system for T-oligo using a nanocomplex formed with an alpha helical peptide for melanoma therapy publication-title: Int. J. Nanomed. contributor: fullname: Uppada – ident: ref76 doi: 10.1016/S0888-7543(02)00033-2 – ident: ref51 doi: 10.18632/oncotarget.10634 – ident: ref74 doi: 10.1053/j.seminhematol.2013.03.030 – ident: ref21 doi: 10.1093/annonc/mdu550 – volume: 5 start-page: 1164 year: 1999 ident: ref47 article-title: Inhibition of telomerase limits the growth of human cancer cells publication-title: Nat. Med. doi: 10.1038/13495 contributor: fullname: Hahn – ident: ref27 doi: 10.1128/MCB.22.1.332-342.2002 – ident: ref63 doi: 10.1096/fj.04-1774com – ident: ref10 doi: 10.1186/s13073-016-0324-x – ident: ref80 doi: 10.1073/pnas.0607332103 – ident: ref31 doi: 10.1016/j.ccr.2004.11.021 – ident: ref9 doi: 10.1016/j.celrep.2013.08.040 – ident: ref16 doi: 10.1038/sj.onc.1205083 – ident: ref20 doi: 10.1038/nrg2763 |
SSID | ssj0000913809 |
Score | 2.3498592 |
SecondaryResourceType | review_article |
Snippet | Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape... |
SourceID | doaj pubmedcentral proquest crossref pubmed |
SourceType | Open Website Open Access Repository Aggregation Database Index Database |
StartPage | 15 |
SubjectTerms | Antioxidants Apoptosis Biological clocks Biomarkers Cancer Cell cycle Cell division DNA damage DNA damage responses G-quadruplex guanine-rich oligonucleotides (GROs) Homeostasis Metastasis Oligonucleotides Proteins Review Senescence shelterin complex Stem cells Telomerase telomere homolog oligonucleotides (T-oligos) Tumors |
SummonAdditionalLinks | – databaseName: DOAJ Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3fS8MwEA7ikz6Iv61OqSC-lS1J0ySPOhxD0KcO9lYubaKCdjI30P_eS9uNVgRffGwuD9e7S-47ev2OkCvAGKAWD5LkRkQYFCbCLEcjyoVLVFLYmnj-4TEZT-L7qZi2Rn35nrCaHrg2XN8msQTEJcYJg3dnrIQBTOED7TA5Jnn9my8VrWKquoM15Wqga1JNjnV9H3zz4KcvPwZ-BG4rCVVc_b8BzJ99kq3EM9olOw1iDG9qTffIhi33yXaLR_CAiLSCfuVTOPROnIfmK0yrFm-_ltrX2ZvFsjqEslg9YfI6JJPRXTocR808hCgXsVxEjNGcKssL4AXVzgBzyhNsGaUcojAHwFAghWTc5qbgDnIKQjuR58YCaH5ENstZaU9ImCinmVE2B13EEEtdMG0qopYYOC4G5HploOy9pr3IsFzwlsw6lgzIrTffepNnq64W0IdZ48PsLx8GpLcyftYcoY-MYm2uEX6qJCCXazEGv_-iAaWdLf0e6SEV5bjnuPbVWhOsJVHMUEPZ8WJH1a6kfHmuCLYxCcRUqtP_eLczssU8EvAzZHSPbC7mS3uOOGZhLqqQ_QYrUvBg priority: 102 providerName: Directory of Open Access Journals – databaseName: ProQuest Central dbid: BENPR link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3dSxwxEA9WX9oHaautZ23Zgvi23OVrkzyVKspRqJRygm_LJJvYQrur5wn63zuzH-edlD5uJg_DTJL5TTL7G8YOAdcAj7iRjPQ6x0Xhc4xyPOdSp8IWVeyI57-fF9ML9e1SX26w6fAvDJVVDmdie1BXTaA78jHHVM0hGrHFGDzdAoTF-Mv1TU79o-idtW-m8YJtCa7owXbr-PT8x8_lfQvxX9qJ62g2JWb6Y6BywntKSCbUFHclLLXs_f-CnM8rJ1dC0dlrtt1jyOxr5_Q3bCPWb9mrFWbBHaZnLRisr7ITcus88w_ZrC36prFZ_NP8jZhoZ1BXwxeGs112cXY6O5nmfYeEPGhlFrkQPHAbZQWy4i55EMkS5Za3NiEuSwACBUYbIWPwlUwQOGiXdAg-Ajj5jm3WTR33WFbY5IS3MYCrFCjjKuF8S92iQOLgiB0NBiqvOyKMEhMIsmS5ZskROybzLScRf3U70Myvyn47lLFQBhBt-qQ9RkRltQcEZhOXEPIUwY7YwWD8st9Ut-XTEhixz0sxbgd644A6Nnc0xxDI4hLnvO98tdQEs0sUC9TQrHlxTdV1Sf37V0u5jWFBcWP3_6_WB_ZSUNSnfjHugG0u5nfxI2KWhf_UL8dHAiLuMA priority: 102 providerName: ProQuest – databaseName: Scholars Portal Open Access Journals dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lj9MwELZQucBhxXsDCwrSilugfsX2ASGoWK2QyqmVeovGid1dqZsupZW6_56ZJO020CPHeBzJmUfm-xTnM2PngDnAAxaSkV5nmBQ-wy7HMy51zG1ehVZ4fvwzv5yqHzM9u5cU6hz4-yi1o_OkpqvFx-2vuy9Y8J-JcSJl_wS0L3BLzGJIv5s_FEoqSvZxh_Sbl7Lj0g5dq7L57129rtSI9x9DnH9vnDzoRBdP2EkHIdOvbcyfsgehfsYeHwgLPmd60mDBep6OKKqr1N-lk2bPN41NwmJ5E5Bnp1BXuyvsZi_Y9OL7ZHSZdQckZKVWZp0JwUtug6xAVtxFDyJaUtzy1kaEZRFAoMFoI2QofSUjlBy0i7osfQBw8iUb1Ms6nLI0t9EJb0MJrlKgjKuE841yiwKJgwn7sHNQcdvqYBTIH8iTRc-TCftG7ttPIvnqZmC5mhddNRQhVwYQbPqoPTZEZbUHxGVDFxHx5KVN2NnO-cUuJQqOZN0hHrV5wt7vzVgN9IkD6rDc0BxDGItLnPOqjdV-JUgu0SxwhaYXxd5S-5b6-qpR3MauoLixr__Hs71hjwRBAzpUxp2xwXq1CW8R2Kz9uyZl_wAt0fi7 priority: 102 providerName: Scholars Portal |
Title | Treating Cancer by Targeting Telomeres and Telomerase |
URI | https://www.ncbi.nlm.nih.gov/pubmed/28218725 https://www.proquest.com/docview/1888992386/abstract/ https://search.proquest.com/docview/1870643136 https://pubmed.ncbi.nlm.nih.gov/PMC5384178 https://doaj.org/article/e647a016bf5b429485ba44109f0716c8 |
Volume | 6 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3Pa9swFH603WU7jO5nvXbBg7Gbm8qSLOnYhpYySCkjhd7Mkyx1hcYpWQrbf78n2Q5J2WmXgCUFxPvh73v28yeAr0gxwDwlkuJWFhQUtiCUYwXjMlS6anwnPD-9qi5vxPdbebsDcvgWJjXtO3t_3D7Mj9v7n6m38nHuxkOf2Ph6OqEkFUzp8S7sKs43SvR0-zWM6xPT6WlyKunHGPsGf8fKg7Avqv9qwjUVD8fegKKk2P8vmvm8W3IDfi724XXPG_PTbn9vYMe3b-HVhprgO5CzRADbu3wSXbnM7Z98lhq949jMPyzmnorrHNtmuCIIew83F-ezyWXRn4pQOCnUqihL5pj2vEHeMBMslkFHmS2rdSAuFhBLmlBSldw72_CAjqE0QTpnPaLhH2CvXbT-APJKB1Na7R2aRqBQpimNTXItAjkNZvBtMFD92Ilf1FQ0RKPWW0bN4Cyab70oalangcXyru49V_tKKCSGaYO0hIJCS4tExk5MIJpTOZ3B0WD8uk-kXzWjCt0QCdVVBl_W05QC8b0Gtn7xFNeoSKwYpzUfO1-tdzL4OgO15cWtrW7PUNQlme0-yj799z8P4WUZSUA8PsYcwd5q-eQ_E4VZ2RG8ODu_uv4xSo8A6Hcq9CiF8V9pn_VV |
link.rule.ids | 230,315,733,786,790,870,891,2115,2236,21416,24346,27957,27958,33779,33780,43840,53827,53829,74659 |
linkProvider | National Library of Medicine |
linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV1Lb9QwEB7B9gAcEG8WWggS4hZ1_YrtE6JVqwXaFUKp1FtkO3aLBEnZbiX67zuTZLe7CHGMx4fRjMfzjTP6BuC9wzPAIgaSFl7leCh8jlmO5UyoVJiijj3x_PGsmJ7IL6fqdHhwuxzaKpd3YndR122gN_JdhqWaRTRiio8Xv3OaGkV_V4cRGndhSwosVUawtXcw-_Z99cpCrJdmYntyTYH1_a6jJsI_VIZMaBTuWjLqOPv_BTT_7pdcS0CHj-DhgByzT72rH8Od2DyBB2t8gk9BlR0EbM6yfXLmPPPXWdm1etNaGX-2vyKW15lr6uUXJrFncHJ4UO5P82EuQh6U1IuccxaYiaJ2omY2eceTIaItb0xCNJac4yjQSnMRg69FcoE5ZZMKwUfnrHgOo6Zt4kvICpMs9yYGZ2vppLY1t74jbJFO4OIYPiwNVF309BcVlg1kyWrDkmPYI_OtNhFrdbfQzs-qIQiqWEjtEGP6pDzmQWmUdwjHJjYh0CmCGcP20vjVEEqX1a3jx_BuJcYgoD8brontFe3RBK2YwD0vel-tNMGaEsUcNdQbXtxQdVPS_DjviLYxGUimzav_q_UW7k3L46Pq6PPs62u4zynv08QYuw2jxfwq7iBqWfg3w9G8Afma7WM |
linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3daxQxEB-0BdEH8bOeVl1BfFvu8rVJnsTWHvXrKHKFvi1JNqmC7tbrFfS_d2Y3d96J-LiZPAyTmcxvssNvAF469AEWMZC08KpEp_AlZjlWMqFSZaomDsTzn2bV8al8f6bOcv_TZW6rXN2J_UXddIHeyMcMSzWLaMRU45TbIk7eTl9f_ChpghT9ac3jNK7DrpaVQg_fPTianXxev7gQA6aZ2IFoU2CtP3bUUPiTSpIJjcXdSEw9f_-_QOffvZMbyWh6B25nFFm8GY79LlyL7T24tcEteB_UvIeD7XlxSAe7KPyvYt63fdPaPH7rvkcstQvXNqsvTGgP4HR6ND88LvOMhDIoqZcl5ywwE0XjRMNs8o4nQ6Rb3piEyCw5x1GgleYiBt-I5AJzyiYVgo_OWfEQdtqujY-gqEyy3JsYnG2kk9o23PqevEU6gYsjeLUyUH0xUGHUWEKQJestS47ggMy33kQM1v1Ctzivc0DUsZLaId70SXnMidIo7xCaTWxC0FMFM4L9lfHrHFaX9R8nGMGLtRgDgv5yuDZ2V7RHE8xiAvfsDWe11gTrSxRz1FBvneKWqtuS9uuXnnQbE4Nk2jz-v1rP4QZ6Zf3x3ezDE7jJCQLQ8Bi7DzvLxVV8igBm6Z9lz_wN_kPxoA |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Treating+Cancer+by+Targeting+Telomeres+and+Telomerase&rft.jtitle=Antioxidants&rft.au=Marko+Ivancich&rft.au=Zachary+Schrank&rft.au=Luke+Wojdyla&rft.au=Brandon+Leviskas&rft.date=2017-02-19&rft.pub=MDPI+AG&rft.eissn=2076-3921&rft.volume=6&rft.issue=1&rft.spage=15&rft_id=info:doi/10.3390%2Fantiox6010015&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_e647a016bf5b429485ba44109f0716c8 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2076-3921&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2076-3921&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2076-3921&client=summon |