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UT research on treatment of triple-negative breast cancer receives $1.4 million funding award - WTVG

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TOLEDO, Ohio (WTVG) - The U.S. Department of Defense has awarded the University of Toledo with a three-year funding award of $1.4 million for a pre-clinical study of promising new chemotherapy aimed at triple-negative breast cancer.

The treatment could be critical in overcoming multidrug resistance that limits therapy options for triple-negative breast cancer. It relies on a unique cell death pathway.

“Triple-negative breast cancer is perhaps the most aggressive, recurrent, and difficult-to-treat breast cancer. Patients with residual, resistant tumors have a six times higher rate of distant recurrence and are 12 times more likely to die. Treatment options are limited and for many patients, the prognosis is extremely poor,” said Dr. Amit K. Tiwari, an associate professor in the UToledo College of Pharmacy and Pharmaceutical Sciences who identified the therapy and is the principal investigator. “Drug discovery is a long road but we have come a significant distance already. We have found a molecule that is safe, effective, and can overcome resistance to other therapeutics.”

Most other chemotherapy drugs kill cancer cells by apoptosis, a process that programs the cells to shrink and break down on multiple fault lines. The compound discovered by Tiwari instead causes cancer cells to swell and burst. When the cells rupture, they release markers that help activate the body’s immune system to target and kill neighboring cancer cells more effectively.

“Our research has shown this drug is killing the cancer cells in multiple different ways,” Tiwari said. “Even the most resistant cancer cells are responding.”

Triple-negative breast cancer accounts for roughly 15% to 20% of all breast cancer cases in the United States. Because the cancer cells present in this type of breast cancer don’t share the receptors that many other forms of breast cancer have, it does not respond to hormonal therapies or therapies that target HER2 receptors.

While traditional chemotherapy may initially work, many patients soon develop resistance to those therapies, allowing the cancer to spread to distant organs unchecked. Tiwari’s research has shown UToledo’s drug appears to be able to treat triple-negative breast cancer even in cases where the cancer cells have developed mutations in the apoptosis signaling pathway and thus resistance to conventional chemotherapy.

The UToledo team has already shown the drug works in animal models and human triple-negative breast cancer cells in the lab. With the Department of Defense funding, researchers will seek to understand the chemical structures necessary to produce unique non-apoptotic cell death and optimize additional analogues of the lead molecule, continue to evaluate its action on patient-derived tumors, and better understand the protein targets that induce cancer cell death.

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