Cedars-Sinai Medical Center Los Angeles United States
The goal of this project is to develop a novel means to inhibit prostate cancer development and progression. The development of Siah12 inhibitors to the ubiquitin ligase Siah12 has been advanced by the ability to develop a Siah12 inhibitory peptide that effectively inhibits Siah12 activity, which was found to effectively attenuate the growth of prostate cancer tumors in vivo when transplanted subcutaneously or orthotopically into the prostate site. The assessment of the Siah12 inhibitory peptide in genetic models of mouse as in human PDX tumors is ongoing by the Partnering PIs Drs. Martin Gleave and Neil Bhowmick at the two respective sites. Parallel development of small molecule inhibitors to Siah2 is on going and will complement the work performed with the inhibitory peptide. This is a first-in class inhibitor of the ubiquitin ligase that can be administered intravenously and that has a notable effect on prostate cancer growth in vivo.