Through studying the 3D structure of the androgen receptor, Researchers in Spain have identified a key protein responsible for its activation. Identifying this protein, called TFIIF, makes it a possible therapeutic target for advanced prostate cancer. You can read the original article here: “Researchers Identify Potential Therapeutic Target for Advanced Prostate Cancer.”
The development and progression of prostate cancer depends on the activation of the androgen receptor (AR) protein. Depriving tumors of androgens, like testosterone, or blocking the AR function are common therapies for prostate cancer. These therapies include anti-androgen drugs, which bind to a specific region of the AR protein thus blocking its activity. However, overtime tumors become resistant to this type of therapy because the protein accumulate alterations and mutates, thus rendering the anti-androgen drugs useless. The patient’s tumor build up a resistance to these therapies after 2-3 years, and develop what’s called castration-resistant prostate cancer (CRPC).
The androgen receptor possess a small region that is important for its activation and survival of the tumor cells. Up until now, this region was not considered a potential target for developing therapies because it was thought to have no relevant structure (which is essential for structure-based drug design.) Now, researchers have discovered that this region recruits the TFIIF protein, and when it binds to the AR it forms the necessary helix shape. These findings show that this interaction, and specifically TFIIF, is a new potential target for CRPC. For prostate tumor cells that have become resistant to treatment, researchers believe that this interaction could be the last mechanism through which the tumor cells survive and proliferate. The researcher team are already searching for drug therapies that interfere with the TFIIF protein.