TARGETING A KILLER Drug discovered in collaboration with College of Pharmacy researchers holds promise for treating an aggressive form of breast cancer. By Melinda Waldrop
Eugenia Broude doesn’t seem particularly vicious. But the assistant professor of pharmacy and her team of researchers are bound and determined to destroy a stubborn cancer. A promising new drug developed in collaboration with Broude and studied by her team in the College of Pharmacy’s SmartState Translational Cancer Therapeutics program and COBRE Center for Targeted Therapeutics is currently being tested in Russia. The targeted clinical trial aims to combat estrogen-positive breast cancers that have proven resistant to anti-estrogen therapy and was designed on the basis of genetic, cellular and animal studies that were conducted by Broude’s team and published earlier this year. “Cancer cells are learning how to grow without hormones, even when conventional anti-hormone drugs are used. They change their program so that they are able to grow anyway,” Broude says. “But our drug is able to block that program, the transcriptional reprogramming that tumors are using to adapt. That’s the Achilles’ heel of the disease. If you take its ability to adapt from cancer, then it will respond better to the drugs.” Broude, who received a doctorate of philosophy from the Ukrainian Academy of Sciences, was recruited to USC six years ago as part of the SmartState research investment program. Her research team works with Senexin B, an orally administered drug discovered by collaborator Senex Biotechnology, a Columbia-based drug discovery and development company focused on oncology therapeutics. The drug was made by Senex as, in collaboration with Broude, the company searched for a way to combat cancer’s ability to hijack surrounding cells for its own deadly purposes. Broude’s lab tested the new drug in combination with drugs traditionally used in breast cancer treatment.
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“We were looking at preventing transcription of previously silent genes in cancer cells, and Senex had tons of drug-like molecules that they sorted, characterized and improved on through chemical modification,” Broude says. “After discovering the mechanism of action of Senexin B, we made a laundry list of things to look for, adding a little bit of this drug and a little bit of that drug to see which of them would work better with Senexin B. “Then we would look at the cells and see if they expressed less of the genes of interest — the bad guys — or if they changed their growth speed, or their size or their shape.” Broude emphasizes that the clinical trial is in the early stages, but the potential of Senexin B, administered in conjunction with traditional drugs, is promising.