James L. Mohler, MD

James L. Mohler, MD

Roswell Park Comprehesive Cancer Center

Buffalo, New York

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.

Articles by James L. Mohler, MD

A Better Abiraterone: The Backdoor Pathway for Intracrine Androgen Metabolism

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.

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Treating a Patient Denied Coverage Based on Not Conforming to NCCN Guidelines

James L. Mohler, MD, Chair of the National Comprehensive Cancer Network (NCCN) Prostate Panel, discusses approaches for urologists dealing with insurance coverage denial for patients who do not fit within NCCN guidelines for prostate cancer. He outlines the iterative, bias-free process of creating the guidelines, which allows for a quick response to the latest research. Dr. Mohler further details how the guidelines value efficacy, quantity/quality of evidence, consistency of evidence, and safety above affordability, and how this can lead to denial of coverage. He then outlines talking points for overcoming guideline-based reasons for rejection from insurance providers.

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Current NCCN Recommendations for Prostate Cancer Genetic Testing

James L. Mohler, MD, discusses the rationale and development of the 2019 NCCN guideline recommendations on genetic testing for prostate cancer. He details the workflow for developing these guidelines and changes for 2019, outlines a new decision-making algorithm for how and when men should be tested, and lays out the panel’s goals and challenges for improving genetic testing.

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