Novel treatment approaches are desperately needed for malignant rhabdoid tumor 
(MRT). Telomerase is an attractive therapeutic target because it is specific to 
cancer and critical for cancer cell immortality. We evaluated the effect of the 
telomerase inhibitor imetelstat in preclinical models of MRT. Three MRT cell 
lines, BT-12, G401, and RT-peri, were treated with the telomerase inhibitor 
imetelstat. The effects of imetelstat on telomere length, DNA damage response, 
and cell proliferation were assessed. The efficacy of imetelstat in vivo was 
evaluated in subcutaneous xenografts derived from each of the cell lines. 
Treatment with imetelstat resulted in inhibition of telomerase activity, marked 
telomere shortening, and activation of the DNA damage response pathway, as 
measured by formation of γ-H2AX nuclear foci, phosphorylation of ATM, and 
phosphorylation of TP53. Imetelstat-treated G401 cells underwent complete growth 
arrest after 16 passages. The other two cell lines exhibited growth inhibition. 
Imetelstat resulted in 40-50% growth inhibition compared to placebo-treated 
controls in all three xenograft models. The activity of imetelstat as a single 
agent suggests that further studies of telomerase inhibitors in combination with 
other agents may be warranted.