Wei Li, PhD, distinguished professor in the Department of Pharmaceutical Sciences at the University of Tennessee Health Science Center and director of the College of Pharmacy’s Drug Discovery Center, has received a $3.24 million grant from the National Cancer Institute. The five-year award will support the development of a new type of therapy for triple-negative breast cancer, one of the most aggressive and difficult-to-treat forms of the disease.
Triple-negative breast cancer accounts for about 10-15% of all breast cancer cases and tends to grow and spread faster than other types. It lacks the common hormone receptors that many breast cancer drugs target, leaving patients with fewer treatment options and a greater risk of recurrence.
Dr. Li’s research focuses on developing a new kind of drug designed to attack a cancer-driving protein often found at high levels in triple-negative breast cancer. This protein, called MDM2, has been linked to faster tumor growth and worse outcomes for patients. Earlier compounds attempted to stop MDM2 by blocking its interaction with p53, a protein that can trigger cancer cell death when freed from MDM2. However, this approach can activate a feedback loop that causes cells to produce even more MDM2, potentially making tumors more aggressive.
Dr. Li’s team is taking a different approach. The researchers have discovered a compound that can break down MDM2 directly, stopping it at the source. In early laboratory models, this new compound has already shown the ability to shrink tumors, offering hope for a more effective treatment.
“This work could lead to an entirely new class of therapies for triple-negative breast cancer,” Dr. Li said. “We’re hopeful that by directly removing the MDM2 protein from cancer cells, we can help more patients respond to treatment regardless of their tumor type.”
The project will move forward with three main goals. First, the team will refine the lead compound to make it even more effective and safer to use. This involves adjusting its structure to improve how well it works in cancer cells and how well it behaves as a medicine in the body. Second, researchers will study exactly how the compound breaks down MDM2 and why that leads to cancer cell death. Understanding the mechanism will help improve the drug’s precision and reduce possible side effects. Third, the team will test how the drug performs in more advanced laboratory models, including studies that simulate how the drug might work in people. They’ll also begin evaluating its safety profile and how the drug moves through and affects the body.
If successful, the research could lead to a first-in-class therapy that opens new treatment pathways not only for triple-negative breast cancer, but potentially other cancers where MDM2 is a key driver.
Dr. Li’s team members at UT Heatlh Science Center include co-investigators Hao Chen, PhD, Department of Pharmaceutical Sciences; Jayaraman Seetharaman, PhD, Department of Pharmacology, Addiction Science, and Toxicology; Hyo Young Choi, PhD, Department of Preventive Medicine; and medicinal consultant Saurin Chokshi, MD, Department of Medicine.