Novel Therapeutic Targets in the Androgen Receptor Signaling Pathway
Prostate cancer is the most common malignancy in men. In 2016, prostate cancer represented 10.7% of all new cancer cases in the U.S. at 181,000. Prostate cancers express the androgen receptor (AR) and rely on androgens for growth and survival. While 80% of patients with prostate cancer respond favorably to initial androgen ablation therapy, most patients experience a relapse of the disease within 1-2 years. Current therapies rely on decreasing the levels of circulating androgens and/or competitively blocking the AR transcription complex. There is a growing body of evidence to suggest that AR signaling also influences tumor cell migration and invasion and provides a novel avenue of future pharmacologic treatment.
The inventors have identified a calcium/calmodulin-dependent protein kinase kinase b (CaMKK-b) that could be a viable therapeutic target for not only treating prostate cancer, but also a variety of other cancers. Provided are methods of screening and identifying a compound that inhibits CaMKK. The inventors show that androgen-mediated migration occurs through a CaMKK-b-AMPK-dependent pathway and pharmacological disruption of this pathway inhibits metastasis and migration of prostate cancer cells. Furthermore, the inventors provide methods to diagnose and detect cancer in a subject, as well as a method for evaluating cancer stage in a subject.
- Novel Method for screening, diagnosing and treating various cancers.
- Provides a method for the production of an antibody that specifically binds to the C-terminal portion of CaMKK-b.
- Currently no other pharmaceutical compound in clinical trials or on the market modulating CaMKK-b.
Duke File (IDF) Number
- McDonnell, Donald
- Frigo, Daniel
- Means, Anthony
- Frigo D, et al. (2011) CaM Kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells. Cancer Res. 71(2):528-37.
For more information please contact
- Gopalakrishnan, Karthik
Interested in this Technology?
Submit your interest below.