Scientists at UTHSC and ORNL Collaborate to Develop Potential New Treatment for Advanced Prostate Cancer

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Ramesh Narayanan, PhD, third from left, and Duane Miller, PhD, second from right, led a team that has identified a possible new treatment for advanced prostate cancer. Also pictured are, from left, Dr. Thamarai Ponnusamy, Thirumagal Thiyagarajan, Dr. Dong-Jin Hwang, at center, and Dr. Yali He, far right. (Photo by Allen Gillespie/UTHSC)

Nearly five years after beginning their research, investigators from the University of Tennessee Health Science Center, with collaboration from scientists at Oak Ridge National Laboratory (ORNL), have found what they believe will be a next generation treatment option for advanced prostate cancer.

Clinical Cancer Research, a high-impact journal in the cancer field, published a paper on the findings this month in its online issue. Ramesh Narayanan, PhD, an associate professor in the Department of Medicine-Hematology in the College of Medicine at UTHSC, is the principal investigator on the project. Duane D. Miller, PhD, professor emeritus in the Department of Pharmaceutical Sciences at UTHSC, is a co-principal investigator on the research.

The UTHSC team identified a novel molecule that binds to the androgen receptors (AR), the receptors for the hormone androgen that fuel prostate cancer growth. This molecule, UT-34, developed at UTHSC and mechanistically studied and defined with the scientific computing capabilities at ORNL, has shown to not only slow the growth of tumors in pre-clinical models, but to shrink them to undetectable size. Vera Bocharova, PhD, and Bobby Sumpter, PhD, directed the work at ORNL.

According to the paper, “this provides the first evidence of the potential of an orally bioavailable AR degrader in advanced prostate cancer.” The findings were validated by an outside contract research firm.

Approximately 18 million individuals are living with prostate cancer today, Dr. Narayanan said. That number is expected to grow to 22 million by 2024. “You have an enormous amount of prostate cancer patients, and under current therapies, these patients respond only for a brief period,” he said. “Most Pharma companies are trying to find the next generation of treatment for advanced prostate cancer.”

He said the UTHSC team has achieved a milestone by identifying these molecules. The next milestone would be the clinical trial process, which he estimates could commence in 12 to 24 months. Depending on those results, a drug could be available in three to five years.

“This makes us really proud,” he said. “I just want to see a drug that’s been developed at UTHSC out there in the market benefiting the patients. We want to see patients getting treated and the cancer being slowed or stopped. That’s what we’re expecting.”

The molecules were licensed to GTx, Inc., which is now Oncternal Therapeutics, through the University of Tennessee Research Foundation (UTRF).

This research was funded by a grant from the National Institutes of Health (NIH), and by grants from GTx, Inc., and Oncternal Therapeutics. Dr. Narayanan was awarded more than $2 million from the NIH in March to continue this research.

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