Daniel P. Petrylak, MD, presented “Novel Ways of Targeting the Androgen Receptor” during the 24th Future Directions in Urology Symposium in August 2024 in Colorado Springs, Colorado.

How to cite: Petrylak, Daniel P. Novel Ways of Targeting the Androgen Receptor.” August 2024. Accessed Dec 2024. https://grandroundsinurology.com/novel-ways-of-targeting-the-androgen-receptor/

Novel Ways of Targeting the Androgen Receptor Summary

Daniel P. Petrylak, MD, explores novel approaches for targeting the androgen receptor (AR) in prostate cancer, highlighting that around 90% of prostate cancer specimens express the androgen receptor, which persists through castrate resistance.

In this 7-minute talk, Dr. Petrylak focuses on targeting the AR ligand-binding domain with molecules known as proteolysis-targeting chimeras (PROTACs). Laboratory findings reveal that PROTACs can degrade AR variants resistant to traditional therapies like enzalutamide, showing efficacy against androgen gene amplification mutations.

He shares that ARV-110, a PROTAC developed for clinical use, showed promise in phase 1 trials with castration-resistant prostate cancer patients. However, due to significant side effects, the ARV-110 trials were abandoned in favor of a newer compound, ARV-766. While ARV-110 has demonstrated efficacy in castration-resistant prostate cancer, ARV-766 offers a broader range of AR degradation with improved patient tolerance, making it the preferred candidate for continued clinical evaluation.

The Future Directions in Urology Symposium (FDUS) is an annual urology think tank and non-CME educational summit that brings together industry figures and experts to discuss the current state of genitourinary care and define future directions in treatment. Dr. Dreicer delivered this educational activity during the 24th iteration of the meeting in August 2024 in Colorado Springs, Colorado.

ABOUT THE AUTHOR

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Daniel P. Petrylak, MD, leads the genitourinary cancers medical oncology team at Smilow Cancer Hospital as director of the genitourinary cancer research group, professor, and co-director of the Cancer Signaling Network program. Dr. Petrylak joined Yale from Herbert Irving Cancer Center at Columbia University Medical Center with New York-Presbyterian Hospital, where he served as Professor of Medicine (Medical Oncology) and Urology and began his appointment in September of 2012. After serving for more than 20 years as the advanced bladder chair for SWOG, Dr. Petrylak is now the Vice Chair of the Genitourinary Committee.