Developing a Novel Therapeutic Strategy Targeting Kallikrein-4 to Inhibit Prostate Cancer Growth and Metastasis
Annual rept. 31 Jul 2014-30 Jul 2015
QUEENSLAND UNIV OF TECHNOLOGY BRISBANE (AUSTRALIA)
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Kallikrein-related peptidase 4 KLK4 is a rational therapeutic target for prostate cancer PCa as it is up-regulated in both localised and bone metastatic tissue, and has been reported to increase PCa cell proliferation, induce epithelial-tomesenchymal EMT-like changes, and could have a role in PCa homing to bone. We therefore hypothesize that blockade of KLK4 activity will inhibit PCa growth and prevent metastasis to secondary sites like bone. This project aims to develop a novel therapeutic strategy targeting KLK4 specifically in PCa. KLK4 siRNA is incorporated into a novel polymeric-based drug-delivery platform currently in development by our laboratory Queensland University of Technologywith collaborators from the Australian Institute of Bioengineering and Nanotechnology AIBN, University of Queensland. In this drug-delivery system, the KLK4 siRNA is conjugated to a hyperbranched polymer HBP backbone, which is also attached at the periphery with a short peptide that binds to prostate specific membrane antigen PSMA expressed on 90 of PCa for prostate-specific delivery of the therapeutic cargo.
- Medicine and Medical Research