Scientists Identify Molecule Driving Triple-Negative Breast Cancer

Researchers at Oregon Health & Science University have developed an experimental molecule named SU212 that targets and breaks down a key metabolic enzyme driving triple-negative breast cancer. According to a study published in the journal Cell Reports Medicine, the compound successfully reduced tumor growth and limited metastasis in humanized mouse models by disrupting how cancer cells process glucose.

Targeting Enolase 1 to Block Cancer Metabolism

Triple-negative breast cancer accounts for roughly 15% of all breast diagnoses, representing an aggressive form of the disease with notoriously limited treatment options. To combat this, the research team focused on an enzyme called enolase 1, or ENO1, which regulates cellular glucose levels and is produced in abnormally high quantities by malignant cells. When the SU212 molecule attaches to ENO1, it forces the enzyme to break down. This disruption starves the tumor of the energy pathways it needs to survive and spread.

“It’s an important step forward to treat triple-negative breast cancer,” said senior author Sanjay V. Malhotra, Ph.D., co-director of the Center for Experimental Therapeutics in the OHSU Knight Cancer Institute, as reported by Oregon Health & Science University. Malhotra also serves as the Sheila Edwards-Lienhart Endowed Chair in Cancer Research and a professor of cell, developmental and cancer biology in the OHSU School of Medicine.

Pathways to Human Clinical Trials and Metabolic Disorders

Moving the experimental molecule toward human clinical trials requires substantial resources to secure Food and Drug Administration approval and launch patient studies. Because SU212 alters glucose metabolism by targeting ENO1, researchers note that this therapeutic mechanism could prove particularly relevant for patients managing metabolic disorders like diabetes, which causes chronically high blood sugar.

The compound itself was originally developed during Malhotra’s earlier research at the National Cancer Institute in Bethesda, Maryland, before his laboratory continued studying the molecule at Stanford University and later at OHSU starting in 2020.

Broader Applications Across Multiple Cancer Types

Beyond triple-negative breast cancer, the research team believes that drugs designed to target enolase 1 could expand the treatment landscape for other malignancies heavily influenced by the same enzyme. According to Oregon Health & Science University, these additional conditions include glioma, pancreatic cancer, and thyroid carcinoma.

“A drug that targets enolase 1 could help improve the treatment of these cancers too,” Malhotra stated.

Funding for the study was provided by multiple National Institutes of Health entities, including the National Cancer Institute, the National Institute on Aging, and the National Heart, Lung and Blood Institute, under award numbers N91019D00024, RF1AG079890, and R01HL164729. Additional support came from the Department of Defense via award HT9425-23-1-0796, alongside the Knight Cancer Institute, the Biomedical Innovation Program at OHSU, and Sheila Edwards-Lienhart endowment funds.