VA Puget Sound Researcher receives Middleton Award
Dr. Stephen Plymate
Dr. Stephen Plymate, an endocrinologist at the VA Puget Sound Health Care System and associate director of the Geriatric Research Education and Clinical Center, has received the 2020 William S. Middleton Award. It is the highest honor conferred by the VA Biomedical Laboratory Research and Development Service.
The Middleton award recognizes Plymate’s groundbreaking contributions to VA research, particularly the field of prostate cancer and its treatment. Prostate cancer is the second most common cancer among men and the leading cause of male cancer deaths. For over 28 years, Plymate has worked to help clinicians better understand which patients will respond to specific prostate cancer treatments, and to develop new drug therapies.
“Dr. Plymate’s work has made a significant, real-world impact in an area that is especially relevant to Veterans' health,” said Dr. Rachel Ramoni, VA chief research and development officer. "His work confirms VA's commitment to excellence in research and treatment of diseases affecting Veterans and patients worldwide."
Plymate is credited with scientific breakthroughs that clarified the biological mechanism underlying lethal, castration-resistant prostate cancer. The growth and spread of prostate cancer cells are driven by male hormones or androgens. One treatment for prostate cancer involves reducing the level of male hormones through drugs, a process referred to as chemical castration. Eventually, prostate cancer cells can become resistant to androgen deprivation therapy. Plymate's discovery of variants in androgen receptor (AR) proteins and the roles they play in treatment-resistant prostate cancers has led to better understanding why traditional therapies fail and how novel therapies can work.
Specific areas of investigation for Plymate include:
The control of prostate cancer growth and metastasis by inhibition of the type 1 insulin-like growth factor receptor (IGF-1R) using human monoclonal antibodies (man-made antibodies synthesized from cloned immune cells). Results in this area over the past year have shown that IGF-IR inhibition markedly enhances effects of castration by altering nuclear localization of the AR by changing AR phosphorylation sites. This work is funded by National Cancer Institute (NCI), National Institutes of Health (NIH).
Research on AR splice variants, which has led to better predictions of patient responses to therapies and more accurate prognoses of advanced prostate cancer. This work is funded by NCI, NCI Specialized Programs of Research Excellence, NIH, Department of Defense Congressionally Directed Medical Research Programs Transformative Grant Award, and a VA-Merit review.
The development of a new drug that can target AR in novel ways that do not involve the ligand binding domain. Plymate's preclinical studies on new compounds such as an orally bioavailable AR inhibitor, Epi-7386, is expected to support an Investigational New Drug filing this year and form the basis of a clinical trial. The trial is expected to have a real-world impact on the treatment of lethal, castration-resistant prostate cancer, a major concern in the Veteran population. Additionally, Plymate has developed new compounds targeting the metabolome of prostate cancer and the VA has participated in patents on some of these compounds.
Plymate is a professor of endocrinology in the department of medicine, director of prostate cancer endocrinology, as well as a founding member of the Institute for Prostate Cancer Research at the University of Washington School of Medicine and Fred Hutchison Cancer Research Center. He is also is also a Veteran himself, having retired at the rank of Colonel from the U.S. Army after 24 years. He has over 230 publications in peer-reviewed journals and is internationally known for his work.
The William S. Middleton Award is awarded annually to senior VA biomedical research scientists in recognition of outstanding scientific achievements in the areas of biomedical and bio-behavioral research. It was established in 1960 to honor Dr. William S. Middleton, distinguished educator, physician-scientist, and VA chief medical director from 1955 to 1963.