American Association for Cancer Research

AACR Award for Outstanding Achievement in Cancer Research

Nima Sharifi, M.D.  34th Annual Award Recipient
Nima Sharifi, M.D.
Kendrick Family Endowed Chair for
Prostate Cancer Research Department of Cancer Biology
The Cleveland Clinic Lerner Research Institute
Cleveland, Ohio

Dr. Sharifi will deliver his award lecture titled Androgen Metabolism Drivers in Prostate Cancer: From Mechanism to Therapy at the Annual Meeting 2014 in San Diego, Calif.  The award ceremony and lecture will be held on Monday, April 7, 2014, from 4:30 p.m. to 5:30 p.m. in the San Diego Convention Center. Visit the AACR Annual Meeting 2014 page for more information.

  • View the list of all prior award recipients.
  • Learn more about the 2014 AACR award recipient.

The Award and Lecture

Through the generous contribution of an anonymous donor, the AACR established this award in 1979 to give recognition to a young investigator on the basis of meritorious achievement in cancer research. In accordance with the wishes of the donor, the recipient must be no more than 40 years of age by the time the award is received.

The recipient of the 34th Annual AACR Award for Outstanding Achievement in Cancer Research will receive an honorarium of $5,000, present a 50-minute lecture, and be given full support for the recipient and a guest to attend the AACR Annual Meeting 2014, in San Diego, Calif., USA (April 5-9, 2014.)

Eligibility

  • Candidacy is open to all cancer researchers who are affiliated with any institution involved in cancer research, cancer medicine, or cancer-related biomedical science anywhere in the world. Such institutions include those in academia, industry, or government.
  • The award will be presented to an individual investigator.
  • Institutions or organizations are not eligible for the award.
  • Candidates must not be more than 40 years of age by the time the award is received. For the 2014 award, a candidate's date of birth must be on or after April 10, 1973.

Nomination Procedure and Instructions

Nominations are closed.

Nominations may be made by any scientist, whether an AACR member or nonmember, who is now or has been affiliated with any institution involved in cancer research, cancer medicine, or cancer-related biomedical science. Candidates may not nominate themselves.

Selection

Candidates for the award will be considered by a prestigious international Selection Committee of renowned cancer leaders appointed by the president of the AACR. The committee will consider all nominations as they have been submitted; the committee may not combine submitted nominations, add a new candidate to a submitted nomination, or otherwise make alterations to the submitted nominations. After careful deliberations by the committee, its recommendations will be forwarded to the Executive Committee of the AACR for final consideration and determination.
Selection of the award recipient will be made on the basis of the candidate's meritorious achievements in cancer research. No regard will be given to race, gender, nationality, or religious or political view.

Questions?

Linda Stokes, Program Associate
American Association for Cancer Research
615 Chestnut Street, 17th Floor
Philadelphia, PA 19106-4404
awards@aacr.org

 

SPOTLIGHT

Nima Sharifi, M.D. 34th Annual Award Recipient
Nima Sharifi, M.D.
Kendrick Family Endowed Chair for
Prostate Cancer Research Department of Cancer Biology
The Cleveland Clinic Lerner Research Institute
Cleveland, Ohio


Dr. Sharifi is recognized for having found that dihydrotestosterone (DHT) synthesis in patients with castration-resistant prostate cancer (CRPC) circumvents the need for testosterone, using instead a previously underappreciated intermediate steroid and for discovering the first gain-of-function mutation in a steroidogenic enzyme, which increases DHT synthesis and drives CRPC.

As a medical oncology and postdoctoral fellow at the National Cancer Institute, Dr. Sharifi focused on the clinical importance of the androgen receptor (AR) as a transcription factor in advanced prostate cancers that are resistant to hormonal therapies; as a result, he has made a significant impact in the field. His interest was captured by the observation of others that prostate cancers become resistant to androgen deprivation therapy by means of a gain-of-function mechanism that essentially reactivates the AR to drive CRPC. A major mechanism required for AR gain-of-function comes into play when tumors acquire the metabolic capability to synthesize their own DHT from adrenal precursor steroids, a capacity that has been clinically validated by FDA-approved next-generation drugs that block the synthesis or effects of DHT, such as abiraterone and enzalutamide.

In 2008, at UT Southwestern, Dr. Sharifi’s  prostate cancer clinic enabled him to take fundamental observations from his laboratory to clinical confirmation in patients with this disease. The generally accepted convention in the field had been that testosterone is an obligate intermediate metabolite that undergoes 5α-reduction to DHT from adrenal precursor steroids in CRPC. In 2011, Dr. Sharifi challenged this dogma and demonstrated that androstenedione, an altogether different steroid, undergoes 5α-reduction to 5α-androstenedione, a previously underappreciated intermediate, en route to DHT. Dr. Sharifi confirmed these findings in fresh metastatic CRPC tissues, obtained with CT-guided biopsies from patients in his clinic using an IRB-approved protocol, to take this story from fundamental biochemistry to clinical confirmation.
 

Also noteworthy, is that elevated DHT concentrations in CRPC was first observed 35 years ago; however, no mutation responsible for this observation had been described. Dr. Sharifi’s recent research identifies the first gain-of-function mutation in a steroidogenic enzyme that increases metabolic flux from steroid precursors to DHT and is responsible for the development of CRPC. This mutation, in 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), blocks the ubiquitination and degradation of this enzyme, increasing its half-life, leading to higher protein levels, and thus increasing metabolic flux in the rate-limiting step from DHEA (the predominant adrenal precursor steroid) to DHT, which in turn stimulates the AR and confers resistance to androgen deprivation therapy.

The significance of these findings may be similar to the discovery of EGFR mutations in non-small cell lung cancer and BRAF mutations in melanoma. Patients with tumors that harbor these gain-of-function enzyme mutations are generally dependent on these genetic lesions, and these tumors are generally responsive to pharmacologic inhibition of these enzymes.
 

Dr. Sharifi is the recipient of a Howard Hughes Medical Institute Physician-Scientist Early Career Award, an American Cancer Society Research Scholar Award, a Prostate Cancer Foundation Young Investigator Award and is also supported by the National Cancer Institute. In 2013, he was appointed the Kendrick Family Endowed Chair for Prostate Cancer Research at the Cleveland Clinic.