| REGULATION
OF HEAT SHOCK PROTEIN 27 IN HORMONE RESISTANT PROSTATE
CANCER.
Dr Charlotte Bevan Imperial College London, Department of Oncology |
 |
The usual treatment for advanced prostate cancer is to use hormone-based therapy. This involves stopping androgens, the natural hormones which cause growth of prostate cells, from working by giving the patient a chemical which to the cells looks similar, but doesn’t cause growth. This is normally successful for a while, but eventually the cancer can return in a form that is resistant to the therapies used.
Recently we carried out a study in prostate cancer cells to see which proteins respond when they are given androgens, as we believe that some of these proteins might be useful targets for designing new drugs to stop prostate cancers from growing.
One protein which responded to androgen is heat shock protein 27. This protein is involved in protecting cells against damage and “cell suicide”, two functions which often go wrong in cancers, allowing them to survive and grow in the wrong circumstances. Heat shock protein 27 has is also present in great quantities in prostate cancers which are resistant to hormone therapy and also in more aggressive prostate cancers.
It is known that cells can change the way heat shock protein 27 works by changing its chemical structure, and it is possible that this structural change causes it to protect the cells against treatment. In some other cancers this change corresponds to aggressiveness of the cancer and we suspect that this may also be the case in prostate cancer. We also think that this change in structure may be part of the way advanced prostate cancers protect themselves against hormone therapy. We therefore wish to measure the changes in heat shock protein 27 structure in prostate cancer cells in the laboratory, both before and after the cells are exposed to androgens to understand exactly how they are altered. We will then create special forms of the protein which cannot be chemically altered, or ones which already have been, and put them into prostate cancer cells to see if they change the way in which prostate cancer cells respond to therapy.
Lastly we will look at prostate cancers from patients to find out if the structure of the heat shock protein 27 in the cancers is different in the early or late cancers, or if certain types of structure are more common in the more aggressive prostate cancers. In the long term, all this information will allow us to use heat shock protein 27 as an indicator of the type of prostate cancer a patient has, and possibly develop drugs which stop it from protecting the cancer cells from therapy.
Progress:
The first interim progress
report (.pdf file) is available here.
Research interim report, 09 April 2008.
Project 2006/09