$3.2 million project targets MDM2 in triple-negative breast cancer

A $3.2 million research effort is developing a promising new treatment for triple-negative breast cancer, one of the most aggressive and difficult-to-treat forms of the disease. The team is developing a new kind of drug designed to attack MDM2, a cancer-driving protein often found at high levels in triple-negative breast cancer, and researchers in early laboratory models said the compound has already shown the ability to shrink tumours.

A researcher at the University of Houston College of Pharmacy has joined the effort, which is led by the Drug Discovery Center at the University of Tennessee Health Science Center College of Pharmacy. The collaboration brings together expertise in chemistry, pharmacology and cancer biology to target MDM2, and $1.7 million has been awarded to support the work in targeting the protein.

Triple-negative breast cancer accounts for between 10 and 15 percent of all breast cancer cases. In clinical terms, triple-negative refers to tumours that test negative for oestrogen receptors, progesterone receptors and excess HER2 protein. Because these cancers lack the common molecular targets used in many breast cancer treatments, options are largely limited to general chemotherapy.

High levels of MDM2 have been associated with faster tumour growth and poorer patient outcomes. Overexpression or amplification of MDM2 has been linked to disease progression and tumor growth, treatment resistance, and poor patient outcomes. Although many MDM2 inhibitors and degraders have been evaluated in clinical trials, there is yet no Food and Drug Administration-approved MDM2 inhibitor on the market.

Researchers identified a compound capable of breaking down MDM2 directly, effectively stopping the protein at its source. The chemistry and drug design work is being led by the Tennessee team, while work in Houston will investigate how the experimental treatment works and evaluate its performance in models that closely resemble human disease.

The team will study how the drug targets MDM2, evaluate the most promising drug candidates to determine effective dosing, understand how the drug behaves in the body, compare it with existing treatments and assess early safety. If successful, the project could lead to a new therapeutic approach for patients facing one of the most challenging forms of breast cancer and help move the potential therapy closer to clinical development for patients who urgently need better options.