Dr. Nima Sharifi from the Cleveland Clinic’s Lerner Research Institute has claimed to have identified a genetic mutation in one of the deadliest forms of prostate cancer. His finding, published online today in the journal Cell, shows that there is a mutation that occurs in an enzyme that is present in a drug resistant form of castration-resistant prostate cancer.

The mutation is responsible for allowing the tumor to make its own supply of androgens, the very hormones that fuels the growth of prostate cancer, even after treatment – medically or surgically – that causes the body to stop producing the hormones.

“When we made the initial observation [of the mutation], we quickly realized what it could mean,” said Dr. Sharifi. It then took an additional three years to identify the mechanism by which the resistance happens, he said.

In laboratory models of human prostate cancer he concluded that prostate cancer cells fall into two categories of androgen synthesis: those that make androgens slowly and those that do so rapidly. His research then found that the mutation explains the difference between the two categories and that DNA from some patient tumors also contains this mutation.

The discovery not only sheds new light on how prostate cancer can change, but it also is helping direct the development of new drugs to block the enzyme, thus preventing prostate cancer from turning deadly.
The finding also adds to current research on a biomarker to predict if a patient’s tumor carries the mutant gene so a more effective treatment can be planned from the beginning.

We have long known that the way prostate cancer tumors become castrate resistant is by making their own hormone, which a tumor needs in order to grow. Hormone treatments (ADT) we use all serve to block the production of androgens or to block their access to the cancer cell. Two of our newest drugs, Zytiga and Xtandi both are “super” versions of our more traditional ADT therapies.

Dr. Sharifi’s finding takes this strategy and theorizes a new and different approach to ADT. First deciding if a man’s prostate cancer is of the genetic structure he identified and then, if it is, to eventually use a yet undeveloped drug to block the suspect enzyme.

This approach is similar to the current approach used in the treatment of melanoma and lung cancer, identifying gene mutations and then targeting the mutation.

Joel T. Nowak, M.A., M.S.W.