Targeting novel protease PRSS23 to inhibit ovarian cancer progression

This project aims to develop a new therapeutic strategy to treat ovarian cancer, by targeting PRSS23, an enzyme that our preliminary data suggest may have a significant role in ovarian cancer growth, progression and metastasis (cancer invasion and spread). PRSS23 has not yet been well-studied, and there are currently no known inhibitors of this enzyme. We propose to determine the structure and firnction of PRSS23, enabling us to create small protein inhibitors that could selectively bind and inhibit the action of PRSS23. We will define the importance of PRSS23 during ovarian cancer growth and metastasis using mouse models of human ovarian cancer, and we will then test our new PRSS23 inhibitors as drugs in these mouse models. We anticipate that our protein-based inhibitors will inhibit PRSS23 produced by tumor cells, while sparing other related proteolytic enzymes, resulting in superior potency for suppressing ovarian cancer spread and recurrence with reduced toxicity compared to other therapeutic strategies. We envision that the protein inhibitors generated from these efforts will become eminently useful in the clinic as antimetastatic therapies and as molecular imaging agents, targeted drug delivery agents, and selective tissue targeting probes.