Researchers at the UVA Cancer Center in a new study have found out how hormones known as androgens work in our cells. This groundbreaking discovery could pave the way in the development better treatments for breast, ovarian and prostate cancers. The results also shed some light on how the gene activity is influenced due to the interaction of androgens with their receptors in cells. This process is crucial in both healthy cells and certain types of cancer. For instance, hormone therapy for prostate cancer aims to reduce the amount of androgens in the body or to prevent it from feeding the cancer cells. However, the therapy doesn’t for some men and for others it eventually fails. Scientists are therefore trying hard to better understand how our healthy cells and cancer interact with androgens. The study reveals a new mechanism by which androgens regulate communication within prostate cancer cells according to Bryce. M. Paschal, PhD, Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine. Anti-androgen therapies are still the keystone of prostate cancer therapy. The better we understand how androgens work, the better researchers will understand why they fail and how even better therapies can be designed in the near future.
In a new article in the journal Nature Communications, Paschal and his colleagues describe how a complex signaling system regulates the activity of androgen receptors. They found that just like a computer reads and write information, the signaling system uses a writer and a reader to modify cellular proteins. Scientists recognized the importance of these modified proteins, but it is difficult to understand how they affect androgen receptors. One key to the regulatory process that Paschal and his team at SOM have found is an enzyme, Parp7, which is produced by the PARP7 gene. Parp7 belongs to a group of enzymes that are involved in important cell functions, including DNA repair.
Certain cancer drugs already target certain Parp enzymes. These drugs are used to treat breast, ovarian and prostate cancer in patients with mutations in DNA repair genes. Androgens are generally discussed in the context of prostate cancer but they are a matter of concern in ovarian and breast cancer also. The results offer new insights into these Parp drugs and could lead to improved treatments that would help patients to get the best results. In addition, Paschal and his team found lower Parp7 levels in prostate cancer that has spread to other parts of the body than in early tumors. This could suggest that a decrease in Parp7 is linked to disease progression, the researchers says.
