CDK5 as a Therapeutic Target in Prostate Cancer Metastasis
Abstract
We have recently found that CDK5 is active in prostate cancer cell lines and in almost all human metastatic prostate cancers, and inhibition of CDK5 activity resulted in reduction of spontaneous metastases by 79%. In this project, we intend to develop CDK5 as a novel therapeutic target. Therefore, we proposed to characterize a series of small molecule CDK5 inhibitors for specificity in cell culture, and for their effect on xenograft models of prostate cancer. We also proposed to examine the role of CDK5 activity in growth of prostate cancer metastatic to bone, using PC3 based bioluminescent cell clones, and to explore the potential for CDK5 inhibition to sensitize prostate cancer cells to chemotherapy. In the current reporting period, we have found that a small molecule derivative of hymenialdisine is a selective inhibitor CDK5, blocking cell motility without an effect on cell growth. This compound may be useful in limiting metastases in prostate cancer. We have also developed the bioluminescent clones of PC3 cells necessary for our proposed examination of the effect of CDK5 inhibition on prostate cancer cell growth in the bone microenvironment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2007
- Accession Number
- ADA471383
Entities
People
- Barry Nelkin
Organizations
- Johns Hopkins University