Targeted Therapy of Human Breast Cancer by 2-5A-Antisense Directed Against Telomerase RNA.

摘要

Targeting telomerase RNA (hTR) for degradation in breast cancer cells using antisense oligonuclotides has demonstrated a high level of cytotoxicity in vitro and in vivo Cell death is rapid and specific to cells expressing telomerase The antisense molecules used in this approach, however, have a number of drawbacks the most critical of which is the relative instability of the molecules which would be an important negative issue for systemic treatment of the disease What these studies have successfully achieved is that they have provided the proof-of-principle that degradation of hTR triggers apoptosis in cancer cells Recently we have investigated the use of small interfering RNA molecules targeting telomerase and demonstrated that they can cause complete degradation of the target hTR within a 2 day period and that this knockdown' can be sustained for up to 6 days Scrambled siRNAs do not have any effect and the targeting siRNA does not affect normal cells which do not express telomerase Preliminary studies suggest that siRNAs also cause extensive cell death over a 4 day period but have the advantage of doing this with only a single treatment Because of the specificity of the siRNA as well as their stability we are transitioning the telomerase targeting project towards using siRNA molecules as a novel therapy for breast cancer.