It could someday also be useful in treating other cancers influenced by the same enzyme, such as glioma, pancreatic cancer, and thyroid carcinoma.
Scientists at Oregon Health & Science University (OHSU) have created a new molecule that could provide a promising path forward in treating some of the most difficult cases of triple-negative breast cancer, a particularly aggressive form of the disease that currently lacks effective therapies.
The findings, published in Cell Reports Medicine, detail how the molecule, called SU212, works by blocking an enzyme that plays a vital role in cancer growth and survival. Researchers tested this approach using a humanized mouse model designed to closely simulate human biological responses.
“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. “Triple-negative breast cancer is an aggressive form of cancer and there are no effective drugs available right now.”
The research team’s next goal is to move SU212 into human clinical trials. This stage will require significant funding, regulatory review by the Food and Drug Administration, and coordinated efforts to begin testing the treatment’s safety and effectiveness in people.
Malhotra, the Sheila Edwards-Lienhart Endowed Chair in Cancer Research and a professor of cell, developmental, and cancer biology in the OHSU School of Medicine, said the molecule could also have a similar role in targeting other forms of cancer in addition to triple-negative breast cancer.
Triple-negative breast cancer accounts for as many as 15% of all breast cancers.
How SU212 Works
Using a humanized mouse model, researchers tested the molecule SU212 against triple-negative breast cancer. The molecule binds to an enzyme known as enolase 1, or ENO1, which regulates glucose levels inside human cells and is overexpressed in cancer cells.
The molecule induced the enzyme to degrade and ultimately suppressed tumor growth and metastasis in the mice.
Normally, the protein functions as part of the body’s metabolic process involved in breaking down glucose to produce energy in the cell. In suppressing the enzyme’s role in cancer cells, Malhotra noted that the effect of SU212 may be especially important in treating cancer patients who also have metabolic diseases like diabetes, a chronic condition causing high levels of blood sugar to build up in the blood.
In addition, he expects SU212 could be useful in treating other cancers influenced by enolase 1, such as glioma, pancreatic cancer, and thyroid carcinoma.
“A drug that targets enolase 1 could help improve the treatment of these cancers too,” he said.
Malhotra arrived at OHSU in 2020 from Stanford University, where his lab continued work on the molecule initially developed during his tenure as a researcher with National Cancer Institute in Bethesda, Maryland.
As co-director of OHSU’s Center for Experimental Therapeutics, Malhotra and colleagues are focused on moving discoveries in the lab as quickly as possible to patients in OHSU’s hospital and clinics. That’s why he came to OHSU in the first place, he said.
“There is definitely great science going on here, and we want to translate that science for the benefit of people,” he said.
Reference: “Non-orthosteric inhibition of enolase 1 impedes growth of triple-negative breast cancer” by Dhanir Tailor, Fernando Jose Garcia-Marques, Abel Bermudez, Annah S. Rolig, Benedikt Grau, Arpit Dheeraj, Dhanya K. Nambiar, Wenqi Li, Kirsten Stefan, Shawn Campbell, Sharon J. Pitteri and Sanjay V. Malhotra, 7 November 2025, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2025.102451
The research was supported by the National Cancer Institute, the National Institute of Aging and the National Heart, Lung and Blood Institute, all of the National Institutes of Health, under award numbers N91019D00024, RF1AG079890, and R01HL164729; the Department of Defense, award HT9425-23-1-0796; the Knight Cancer Institute and the Biomedical Innovation Program at OHSU; and Sheila Edwards-Lienhart endowment funds.
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