Prostate Cancer Awareness Month: Exciting Developments

In recognition of September as Prostate Cancer Awareness Month, Daniel Petrylak, MD, professor of oncology and urology at Yale School of Medicine, discusses what he's most excited about in the field of prostate cancer treatment.

Petrylak is excited by an upcoming clinical trial at Yale, described an innovative drug called a PROTAC, which stands for proteolysis-targeting chimera. The drug was developed on the Yale campus and represents a paradigm shift in pharmacology. Unlike traditional medications that often inhibit a protein's function, PROTACs work by hijacking the cell's natural protein degradation system.

Petrylak explains that the PROTAC functions like a "molecular matchmaker." It brings the target protein, in this case, the androgen receptor, into close proximity with a cellular machine called the proteasome. The proteasome is essentially the cell's recycling center, responsible for breaking down and disposing of damaged or unnecessary proteins. The PROTAC acts as a flag, marking the androgen receptor for destruction. This process is a natural part of cell biology, but the drug significantly accelerates it.

Petrylak also highlights early data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting that showed promising results for a specific PROTAC, ARV-766, which demonstrated activity in patients with mutations in their androgen receptors. This is a significant development, as these mutations can often render traditional hormone therapies ineffective.

Petrylak also notes another intriguing discovery related to PROTACs. They found that these drugs cause a robust upregulation of prostate-specific membrane antigen (PSMA). This finding led to the design of a new clinical trial at Yale that will combine a PROTAC with lutetium PSMA, a type of targeted radiotherapy. The hope is that the PROTAC's ability to increase PSMA expression will make the lutetium PSMA more effective at targeting and destroying cancer cells. Petrylak concludes by emphasizing the potential of this combination therapy to improve treatment outcomes for patients.

Read the full interview with Dr Petrylak here.