Elucidating the Function of a New Tumor Suppressor in Prostate Cancer Progression

Principal Investigator: CICHOWSKI, KAREN
Institution Receiving Award: BRIGHAM AND WOMEN'S HOSPITAL, INC.
Program: PCRP
Proposal Number: PC074048
Award Number: W81XWH-08-1-0149
Funding Mechanism: Idea Development Award
Partnering Awards:
Award Amount: $622,500.00


If detected early, prostate cancer is treatable. However, there are currently no effective therapies for advanced disease. Accordingly, identifying the genes and elucidating the mechanisms involved in the progression of prostate cancer will not only provide important insight into the tumorigenic process, but will ultimately lead to new therapeutic strategies. In addition, developing a genetically accurate animal model of metastatic disease will enable us to rapidly test and identify effective therapies, which will undoubtedly inspire and inform clinical trials.

While many of the genetic changes that underlie prostate cancer are known, there are certainly more to be identified. In particular, very little is known about the genes/signals that promote metastasis. We recently identified a gene that we believe is a new tumor suppressor in human prostate cancer. Interestingly, this gene has been reported to be inappropriately "turned off" in a variety of advanced human cancers. Moreover, this gene appears to function as a "signaling hub" capable of coordinating a variety of cancer promoting signals. Our central hypothesis is that this gene is involved in prostate cancer progression and may specifically drive the metastatic process.

To test this, we will develop several types of animal models. These studies will be useful for precisely determining how this gene functions. However, these studies will not just inform us about one gene but should also identify the critical downstream pathways that are likely to be deregulated in all metastatic tumors. This line of research will undoubtedly lead to new therapeutic targets for the treatment of metastatic disease. It may also result in the identification of new diagnostic markers. Finally, the mouse models that will be generated should facilitate therapeutic testing and development.