TY - JOUR
T1 - A novel telomerase substrate precursor rapidly induces telomere dysfunction in telomerase positive cancer cells but not telomerase silent normal cells
AU - Mender, Ilgen
AU - Gryaznov, Sergei
AU - Shay, Jerry W.
N1 - Funding Information:
I. Mender was supported by Scientific and Technological Research Council of Turkey (TUBITAK). These studies were supported in part by NCI SPORE P50CA70907, the Simmons Cancer Center Support Grant 5P30 CA142543 and support from the Southland Financial Corporation Distinguished Chair in Geriatric Research (J.W.S. and W.E.W.). This work was performed in space constructed with support from National Institute of Health grant C06 RR30414. We thank Dr. Cynthia Lander for valuable discussions.
PY - 2015
Y1 - 2015
N2 - Although telomerase is an almost universal target for cancer therapy, there has been no effective telomerase targeted inhibitor that has progressed to late stage human clinical trials. Recently, we reported that a telomerase-mediated telomere-disrupting compound, 6-thio-2'-deoxyguanosine (6-thio-dG), was very effective at targeting telomerase positive cancer cells while sparing telomerase silent normal cells. 6-thio-dG, a nucleoside analogue of the already-approved drug 6-thioguanine, is incorporated into telomeres by telomerase, resulting in disruption of the telomere-protecting shelterin complex. This disruption leads to Telomere dysfunction-Induced Foci (TIFs) formation and rapid cell death for the vast majority of cancer cells. Since most chemotherapies eventually fail due to drug acquired resistance, novel drugs such as 6-thio-dG, as a single first line agent or in the maintenance setting, may represent an effective new treatment for cancer patients.
AB - Although telomerase is an almost universal target for cancer therapy, there has been no effective telomerase targeted inhibitor that has progressed to late stage human clinical trials. Recently, we reported that a telomerase-mediated telomere-disrupting compound, 6-thio-2'-deoxyguanosine (6-thio-dG), was very effective at targeting telomerase positive cancer cells while sparing telomerase silent normal cells. 6-thio-dG, a nucleoside analogue of the already-approved drug 6-thioguanine, is incorporated into telomeres by telomerase, resulting in disruption of the telomere-protecting shelterin complex. This disruption leads to Telomere dysfunction-Induced Foci (TIFs) formation and rapid cell death for the vast majority of cancer cells. Since most chemotherapies eventually fail due to drug acquired resistance, novel drugs such as 6-thio-dG, as a single first line agent or in the maintenance setting, may represent an effective new treatment for cancer patients.
KW - 6-thio-2'deoxyguanosine
KW - 6-thioguanine
KW - Cancer
KW - Telomere induced foci
KW - Telomere shortening
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U2 - 10.18632/oncoscience.213
DO - 10.18632/oncoscience.213
M3 - Article
C2 - 26425659
AN - SCOPUS:84959261141
SN - 2331-4737
VL - 2
SP - 693
EP - 695
JO - Oncoscience
JF - Oncoscience
IS - 8
ER -