Nature Communications Publishes Desai Sethi Discovery That Could Transform Prostate Cancer Treatment
Summary
- Nature Communications has published a University of Miami Miller School of Medicine study that could explain why prostate cancer progresses despite treatment with androgen deprivation therapy.
- Prostate cancer affects one in eight men in the U.S. and is the second leading cause of cancer death in men in the country.
- The novel finding stands to transform the way we think about androgen deprivation therapy, one of the mainstays of prostate cancer treatment.
Nature Communications has published a study led by Nima Sharifi, M.D., Desai Sethi Urology Institute (DSUI) scientific director and a member of Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, that uncovers a previously unknown pathway that could explain why androgens remain and prostate cancer progresses despite treatment with androgen deprivation therapy.
The novel finding stands to transform the way we think about androgen deprivation therapy (ADT), one of the mainstays of prostate cancer treatment. ADT has relied on blocking the androgen synthesis enzyme CYP17. The CYP17 pathway has been known and characterized since 1966. It’s “textbook physiology,” according to Dr. Sharifi.
Researchers in this study uncovered a different, parallel pathway that current medicines do not target.
“The big takeaway here is that this may be an entirely new and independent pathway that we need to figure out how to block in order to treat prostate cancer more effectively,” said Dr. Sharifi, also professor of urology at the Miller School.
Current Prostate Cancer Treatment
Prostate cancer affects about one in eight men during their lifetime and is the second-leading cause of cancer death in American men, according to the American Cancer Society. Doctors prescribe ADT in advanced prostate cancer to deprive the cancer of testosterone, which promotes tumor growth.
“Androgen deprivation therapy has been part of prostate cancer treatment for more than 80 years,” Dr. Sharifi said. “One of the more modern medicines that blocks androgens from gonadal and nongonadal sources is abiraterone, which blocks androgens made from CYP17. It has been FDA-approved for about 15 years, is used worldwide and has a very clear role and benefit in the treatment of prostate cancer.”
The problem with the current treatment is two-fold, according to Dr. Sharifi. First, patients have tumors that become resistant. Also, studies that look at inside prostate cancer tissue show that androgens remain, despite therapy.
“Since we’ve used abiraterone in the clinic, the field has struggled with wondering if there is a better way to block the same enzyme or if blockade of CYP17 isn’t the whole solution,” Dr. Sharifi said.
A Genetic Approach to Prostate Cancer
There was no established path when conducting this study. Dr. Sharifi described work by coauthor Ziqi Zhu, Ph.D., research assistant professor of urology at the Miller School, as similar to searching in a dark room without knowing the target of your search.
‘’’First, we addressed this challenge directly, through chemical and biochemical methods. Next, we used a series of genetic approaches in combination with biochemistry. Basically, we expressed every known enzyme in this family to figure out what else can do this,” Dr. Sharifi said. “In a way, we believe the study is so important because it bucks the dogma.”
“Androgens play a central role in prostate cancer, and therapies that block androgen synthesis have saved thousands of patients,” said Dr. Zhu. “By combining inhibitors of the known enzymes with those targeting the enzymes that we discovered, it may be possible to help even more patients.”
Next Steps
Research, including pre-clinical models, demonstrates CYP51 is a different pathway that skirts known drug targets for prostate cancer and contributes to prostate cancer progression. The next step is to figure out how this finding might be important to the care of men with prostate cancer, according to Dr. Sharifi.
The findings have broad implications for patient care beyond prostate cancer.
“There are a lot of aspects of physiology and disease that are important outside of cancer where this discovery may shed additional light,” Dr. Sharifi said. “This includes non-cancer implications for anything related to androgens or estrogens and disease.”
Tags: cancer research, clinical trials, Desai Sethi Urology Institute, Dr. Nima Sharifi, Dr. Ziqi Zhu, Newsroom, prostate cancer, Sylverster Comprehensive Cancer Center, USNWR Urology, USNWR Urology 2026