Scientists discover new molecule that kills hard-to-treat cancers

A new molecule synthesized by a University of Texas at Dallas researcher kills a broad spectrum of hard-to-treat cancers, including triple-negative breast cancer, by exploiting a weakness in cells not previously targeted by other drugs.

A study describing the research — which was carried out in isolated cells, in human cancer tissue and in human cancers grown in mice — was published online June 2 in the journal Nature Cancer.

Dr. Jung-Mo Ahn, a co-corresponding author of the study and a UT Dallas associate professor of chemistry and biochemistry in the School of Natural Sciences and Mathematics, has been passionate about his work designing small molecules that target protein-protein interactions in cells for over a decade. Using an approach called structure-based rational drug design, he previously developed potential therapeutic candidate compounds for treatment-resistant breast cancer and for prostate cancer.

In the current work, Ahn and his colleagues tested a novel compound he synthesized called ERX-41 for its effects against breast cancer cells, both those that contain estrogen receptors (ERs) and those that do not. While there are effective treatments available for patients with ER-positive breast cancer, there are few treatment options for patients with triple-negative breast cancer (TNBC), which lacks receptors for estrogen, progesterone and human epidermal growth factor 2. TNBC generally affects women under 40 and has poorer outcomes than other types of breast cancer.

“The ERX-41 compound did not kill healthy cells, but it wiped out tumor cells regardless of whether the cancer cells had estrogen receptors,” Ahn said. “In fact, it killed the triple-negative breast cancer cells better than it killed the ER-positive cells.

“This was puzzling to us at the time. We knew it must be targeting something other than estrogen receptors in the TNBC cells, but we didn’t know what that was.”

To investigate the ERX-41 molecule, Ahn worked with collaborators, including co-corresponding authors Dr. Ganesh Raj, professor of urology and pharmacology at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, as well as Dr. Ratna Vadlamudi, professor of obstetrics and gynecology at UT Health San Antonio. Dr. Tae-Kyung Lee, a former UTD research scientist in Ahn’s Bio-Organic/Medicinal Chemistry Lab, was involved in synthesizing the compound.

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