Dr. Ralf Kittler, Assistant Professor of Pharmacology, studies ERG, a protein that facilitates the transformation of normal prostate cells into cancer cells. His lab found that an enzyme called USP9X protects ERG from degradation and subsequently found that a molecule called WP1130 can block USP9X and lead to the destruction of ERG.
"We now have a target that we could potentially exploit to develop a drug for treatment," said Dr. Kittler, UT Southwestern's first Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research.
The findings are published in the Proceedings of the National Academy of Sciences. Dr. Kittler's team tested the molecule successfully in mice, but the process needs to be improved to be effective in humans, he said. Toxicity and side effects also will be tested, so much work lies ahead, and it could take many years before knowing whether the molecule can be developed into a drug that is effective in humans.
"It's a good start, and now we are in a position to develop the finding further in an effort to move into the clinic," said Dr. Kittler, the John L. Roach Scholar in Biomedical Research of UT Southwestern's Endowed Scholars Program.
The observation may represent an important advance against one of the major cancer killers. Prostate cancer is the most common type of cancer in men and the second most common cause of male cancer death in the United States. The disease caused nearly 30,000 deaths in 2013, according to the American Cancer Society.
Metastatic prostate cancer currently is treated with drugs that inhibit a protein called Androgen Receptor. This treatment initially halts cancer growth, but eventually the cancer becomes resistant to the drugs. Dr. Kittler's findings offer a new avenue of research.
Dr. Kittler's research was supported by CPRIT. Other UT Southwestern researchers involved include Dr. Payal Kapur, Associate Professor of Pathology and Urology; Dr. Yair Lotan, Professor of Urology; Dr. Ganesh Raj, Associate Professor of Urology; and Dr. Jer-Tsong Hsieh, Professor of Urology.
Dr. Kittler holds a joint appointment in the Eugene McDermott Center for Human Growth and Development, and is a member of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
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