A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism

Posted by James L. Mohler, MD | Jul 2020

James L. Mohler, MD, presented “A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism” during the 30th Annual International Prostate Cancer Update on January 23rd, 2020 in Beaver Creek, Colorado.

How to cite: Mohler, James L. “A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism” January 23rd, 2020. Accessed Apr 2024. https://grandroundsinurology.com/a-better-abiraterone-the-backdoor-pathway-for-intracrine-androgen-metabolism/

A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism – Summary:

James L. Mohler, MD, Associate Director and Senior Vice President for Translational Research and Professor of Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York, discusses the cause of and potential solutions to androgen receptor expression in castration-recurrent prostate cancer. He explains that prostate cancer tissue in a patient with castration-recurrent disease actually has greater levels of testosterone than benign prostate tissue and that castration-resistant prostate cancer relies on a backdoor pathway of manufacturing testosterone by which dihydrotestosterone (DHT) is made from androstanediol. Abiraterone is intended to inhibit CYP17A1 and therefore prevent the manufacture of DHT, but Dr. Mohler suggests that abiraterone inhibits CYP17A1 that is too far from DHT synthesis to achieve long term response by inhibition. He then discusses current research about a promising drug that targets the catalytic domain shared by the five 3α-oxidoreductases associated with DHT production.

About The 30th Annual International Prostate Cancer Update:

The International Prostate Cancer Update (IPCU), founded in 1990, is a multi-day CME conference focused on prostate cancer treatment updates with expert, international faculty. It is led by expert physicians and is designed for urologists, medical oncologists, radiation oncologists, and other healthcare professionals involved in the diagnosis and treatment of prostate cancer. Dr. Mohler gave this presentation during the 30th iteration of the meeting in January 2020.

For further educational activities from this conference, visit our collection page.

About The Author

James L. Mohler, MD

James L. Mohler, MD, is the Associate Director and Senior Vice President for Translational Research, the Chief of Inter-Institutional Academics, and a Professor of Oncology at Roswell Park Comprehensive Cancer Center in Buffalo, New York. He also serves as Professor of Urology at the University of Buffalo School of Medicine and Biomedical Sciences and Adjunct Professor of Urology and Member of UNC-Lineberger Comprehensive Cancer Center at the University of North Carolina. Dr. Mohler has been engaged in translational research for over 30 years. His activities have largely focused on the role of the androgen receptor (AR) in prostate cancer (CaP) recurrence after androgen deprivation therapy (ADT), as well as racial differences in CaP aggressiveness. These research activities include the Program Project-funded “Prostate Cancer: Transition to Androgen-Independence” and the DOD Prostate Cancer Research Program-funded “North Carolina-Louisiana Prostate Cancer Project (PCaP),” the largest population-based CaP study ever conducted (2258 men with newly diagnosed CaP at 11 institutions). PCaP sought to compartmentalize the reasons for increased CaP mortality in African Americans. Thus far, racial differences in interactions between African American CaP patients and the American Healthcare System seem to outweigh the impact of racial differences in CaP biology and both the host’s environment (diet) and genetics. PCaP’s P01 demonstrated that tissue levels of dihydrotestosterone (DHT) in CaP that recurs during ADT are sufficient for AR activation, which leads to the re-purposing of abiraterone to treat castration-recurrent CaP. Dr. Mohler’s focus on AR and ADT continues with 2 grants to support the characterization of the 3 pathways for intracrine metabolism of testosterone and DHT, as well as a novel therapeutic against DHT production. His focus on racial disparities in CaP continues with a new grant to study financial distress.

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