The role and regulation of glycogen synthase kinase-3 in prostate cancer

Dr Robert Kypta, CIC bioGUNE, Spain

The androgen receptor (AR) is a cellular protein that binds the main male hormone, and through its activity controls prostate cancer growth.  We have found that GSK3, an enzyme that adds a phosphate molecule to other proteins involved in sugar metabolism and many other body processes increases the activity of AR in prostate cancer.  We also showed that GSK3 inhibitors reduce the growth of prostate cancer cells.  Those inhibitors are not soluble enough to be used in patients, but pharmaceutical companies are developing new GSK3 inhibitors for the treatment of diabetes and Alzheimer's disease and we hope to use these in the future.  However, we first must find out exactly how GSK3 activates AR and which of the two related GSK3 subtypes is more important for prostate cancer.  We propose to make antibodies that can be used to identify patients who have prostate tumours with the active form of GSK3 and would be candidates for GSK3 inhibitor therapy.  The antibody would also be used to monitor if a GSK3 inhibitor is working as predicted.  This is a basic research project and is not anticpated to make a difference to patients during the lifetime of this grant.  However, a best-case scenario is that, three years from now, GSK3 inhibitors will be approved for treatment of diabetes or Alzheimer's disease.  We would then test those inhibitors in cell culture and animal models for prostate cancer, using our antibodies to monitor their effects, and select the most effective inhibitors for clinical trials.

Project commenced

January 2009

Length of project

1 year initially

Amount supported

£39,527