Nima Sharifi, MD, to Receive the 2021 AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research

PHILADELPHIA – The American Association for Cancer Research (AACR) is recognizing Nima Sharifi, MD, with the 2021 AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research.

Sharifi is director of the Center for Genitourinary Malignancies Research at Lerner Research Institute at the Cleveland Clinic; the Kendrick Family Endowed Chair for Prostate Cancer Research at the Cleveland Clinic; and a professor in the Department of Molecular Medicine at Case Comprehensive Cancer Center at Case Western Reserve University in Cleveland. He is being honored for his pivotal contributions to the understanding of how steroid metabolism contributes to prostate cancer progression, defining the first example of a gain-of-function steroidogenic enzyme missense mutation that permits dihydrotestosterone (DHT) synthesis from adrenal precursors. In a series of clinical studies, he illustrated that this missense mutation represents an effective predictive biomarker in castration-resistant prostate cancer. His findings have since been validated by researchers worldwide.

“Dr. Sharifi is an outstanding physician-scientist whose discoveries have had a significant impact on our understanding of prostate cancer biology and therapeutics. He is renowned for his ability to make observations in fundamental biochemistry and then translate them into the clinic,” said Margaret Foti, PhD, MD (hc), chief executive officer of the AACR. “We are proud to honor the memory of our dear colleague, friend, and mentor, AACR Past President Waun Ki Hong, MD, FAACR, by celebrating the pioneering achievements of Dr. Sharifi with this prestigious award.”

In 2017, the AACR instituted the AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research to recognize a worthy cancer researcher who has conducted highly meritorious translational and clinical cancer research anywhere in the world, and who has not yet reached 51 years of age at the time of award presentation. The award was established in recognition of the extraordinary contributions that Hong, a Fellow of the AACR Academy, made to advances in cancer research, cancer care, and cancer prevention during his long-standing and brilliant career as a physician-scientist.

Sharifi has made significant contributions to cancer research through his focus on the role of androgen synthesis in advanced castration-resistant prostate cancers. Early in his career, he challenged the generally accepted dogma that testosterone is an obligate intermediate metabolite that undergoes a 5α-reduction to form DHT from adrenal precursor steroids in castration-resistant prostate cancer. He demonstrated that a different steroid, androstenedione, is also capable of undergoing a 5α-reduction to form 5α-androstanedione and eventually DHT, thus driving tumor progression.

Although it was already known that DHT in castration-resistant prostate cancer is capable of driving androgen receptor function, no specific mutation had been identified until Sharifi described the first gain-of-function mutation in 3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1, which leads to greater enzyme levels and increases the metabolic flux from steroid precursors to DHT, in turn contributing to the development of castration-resistant prostate cancer.

Tumors that harbor HSDB1 mutations are generally dependent on these genetic lesions and are often responsive to pharmacologic inhibition. Sharifi has shown that in patients with prostate cancer treated with androgen deprivation therapy, those who inherit such enzyme variants develop resistance much more rapidly. He has also demonstrated that such missense mutations represent predictive rather than prognostic biomarkers, and in a phase III trial for patients with low-volume metastatic prostate cancer, he demonstrated that the HSDB1 variant is indeed a predictive biomarker for response to androgen deprivation therapy.

Sharifi, an AACR member since 2006, currently serves as a member of the AACR Award for Outstanding Achievement in Chemistry in Cancer Research Committee. He was previously honored by the AACR in 2014 with the AACR Outstanding Achievement in Cancer Research Award.

Sharifi has received numerous other awards and accolades throughout his career, including the Maria and Sam Miller Award for Scientific Achievement (2019); the Richard E. Weitzman Outstanding Early Career Investigator Award of the Endocrine Society (2017); the Awards for Outstanding Mentor and Outstanding Science from the Lerner Research Institute at the Cleveland Clinic (2016); the American Cancer Society Research Scholar Award (2012); the Howard Hughes Medical Institute Physician-Scientist Early Career Award (2009); and the Prostate Cancer Foundation Young Investigator Award (2008). He was elected as a member of the Association of American Physicians (2018); as a fellow of the American Association for the Advancement of Science (2017); and as a member of the American Society for Clinical Investigation (2014).

He received his bachelor’s degree from Virginia Tech in Blacksburg, and his medical degree from the University of Pittsburgh School of Medicine in Pennsylvania. He completed his residency at Yale-New Haven Hospital in Connecticut and a fellowship at the National Cancer Institute in Bethesda, Maryland.