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.