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Prevention of prostate cancer growth and spread achieved in animal studies

Researchers at Georgetown Lombardi Comprehensive Cancer Center have completed a critical step in the journey from a basic science discovery in the lab to a potential clinical application, showing that an experimental agent prevents tumor growth and spread in mice with prostate cancer harboring a common chromosomal abnormality.

Published online in PLOS ONE, the scientists say the agent, YK-4-279, is the first drug targeted at the chromosomal translocations found in about half of prostate cancer cells. These translocations occur when two normal genes break off from a chromosome and fuse together in a new location. This so-called ETS fusion produces new genes that manufacture proteins, which then push prostate cancer cells to become more aggressive and spread.

“Having a compound that works in mouse models brings us closer to early phase human clinical trials,” says the study’s lead investigator, Aykut Üren, MD, associate professor of molecular oncology at Georgetown Lombardi. “However, we are only mid-way through that process. We need to establish the potential side effects and figure out the best way to administer this compound in a human clinical study.”

Üren and his colleagues used two prostate cancer lines growing in immunocompromised mice. “YK-4-279 was very effective against the mice with ETS fusion and was not effective against the mice without it,” Üren reports. “That demonstrated to us the specificity with which the drug works, and gave us a good reason to expect a similar response in patients with ETS fusion-positive prostate cancer in future clinical trials.”

The researchers also found that mice tolerated long-term treatment (6-12 weeks), and that YK-4-279 inhibited both the growth of the primary tumor and spread of the cancer to the lungs.

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YK-4-279 was designed in the GUMC Drug Discovery Program, directed by Milton Brown, MD, PhD, a co-author on the paper. YK-4-279 is also being investigated for the treatment of Ewing’s sarcoma, a rare childhood cancer.

Additional Georgetown University Medical Center co-authors are Said Rahim, PhD, Tsion Minas, Sung-Hyeok Hong, DVM, PhD, Sarah Justvig, Haydar Çelik, PhD, Yasemin Saygideger Kont, MD, Jenny Han, Abraham T. Kallarakal, PhD, Yali Kong, PhD, Bhaskar Kallakury, MD and Jeffrey A. Toretsky, MD. Michelle A. Rudek, PhD, from Johns Hopkins University is also an author.

A Department of Defense Synergistic Idea Development Award (W81XWH-12-1-0398) funded the study.

Georgetown University is owner of patented intellectual property described in the paper. Üren and Georgetown co-authors Brown, Kong, and Toretsky are named as co-inventors on the patent. Georgetown University has licensed the technology for commercialization. Toretsky has a minority ownership interest in the company that has licensed the technology and he occasionally serves as a consultant.

Georgetown University Medical Center