Telomerase is required for cell immortality, a hallmark of cancer, and is expressed in majority of cancer types, but not in most normal adult tissues. Therefore, inhibition of telomerase is a promising anti-cancer treatment strategy. GRN163L, a lipidated oligonucleotide with potent telomerase inhibitory activity, is currently in Phase I/II clinical trials in solid tumor and hematological cancers. The target effect of GRN163L is presently being monitored by measuring inhibition of telomerase activity in GRN163L-treated samples. In addition, sensitive detection of telomere shortening is a highly desirable pharmacodynamic measurement. In this study, we used a PCR-based telomere length assay to detect a marked decrease in telomere lengths in GRN163L-treated bulk myeloma tumor cells and putative cancer stem cells after 3 weeks of in vitro treatment. This assay was also adapted to evaluate the effects of GRN163L on telomere lengths in mouse xenograft tumors. Preliminary data suggested that, compared to vehicle control treatment, GRN163L treatment of xenograft tumor-bearing animals was associated with an accumulation of shortened telomeres in the tumors. Our data provide evidence that treatment of human tumor cell lines in vitro and in vivo with GRN163L can result in telomere shortening, which is a predicted pharmacodynamic response to telomerase inhibition-based therapeutic intervention. Our results also demonstrate the utility of a PCR-based telomere length assay in the non-clinical setting.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3482.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009