Targeting STAMP2 and KLK4 for prostate cancer therapy (copy)

Our laboratory is studying proteins that are implicated in the progression of prostate cancer (PCa). KLK4 and STAMP2, encoded by two androgen regulated genes, play important roles in PCa progression documented by our group. siRNAs targeting KLK4 (Jin et al. PNAS 2013) or STAMP2 (Jin et al. EMBO Mol Med. 2015) inhibit PCa cell growth both in vitro and in vivo. In particular, we have shown that nanoliposomal siRNA for KLK4 or STAMP2 that are systemically introduced into mice harboring human PCa tumors by the tail vein results in dramatic tumor regression. To take this further, for potential clinical applications, we have now screened approximately 50 potential siRNAs targeting either KLK4 or STAMP2 and identified 4-5 siRNAs with very low IC50 for both targeting and cell killing (in 3 different PCa cell lines) in vitro. Furthremore, in a previous project (FOTS 8411), we tested these siRNAs in the LNCaP xenograft model and observed promising effect. Therefore, we would like to repeat the experiment in another xenograft model VCaP and determine if this may be a general effect across different PCa preclinical mouse models.