Highly specific targeting of the TMPRSS2/ERG fusion gene using liposomal nanovectors

使用脂质体纳米载体高度特异性地靶向 TMPRSS2/ERG 融合基因

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作者:Longjiang Shao, Ibrahim Tekedereli, Jianghua Wang, Erkan Yuca, Susan Tsang, Anil Sood, Gabriel Lopez-Berestein, Bulent Ozpolat, Michael Ittmann

Conclusions

Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer.

Purpose

The TMPRSS2/ERG (T/E) fusion gene is present in half of all prostate cancer tumors. Fusion of the oncogenic ERG gene with the androgen-regulated TMPRSS2 gene promoter

Results

The targeting siRNAs were both potent and highly specific in vitro. In vivo they significantly inhibited tumor growth. The degree of growth inhibition was variable and was correlated with the extent of fusion gene knockdown. The growth inhibition was associated with marked inhibition of angiogenesis and, to a lesser degree, proliferation and a marked increase in apoptosis of tumor cells. No toxicity was observed. Conclusions: Targeting the T/E fusion junction in vivo with specific siRNAs delivered via liposomal nanovectors is a promising therapy for men with prostate cancer.

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