Researchers at Oregon Health & Science University have developed a new molecule that may open the door to treating difficult cases of triple-negative breast cancer, a particularly aggressive form of the disease that currently has few effective treatment options.
In a study published in the journal Cell Reports Medicine, the team describes how the experimental molecule, called SU212, blocks an enzyme that plays a key role in cancer progression. The findings come from experiments using a humanized mouse model designed to mimic human disease.
“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 next stage of development would involve moving the molecule toward human clinical trials. That process requires significant resources to obtain Food and Drug Administration approval and to launch studies involving patients.
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 same strategy could potentially be used to treat other types of cancer as well.
Triple-negative breast cancer makes up about 15% of all breast cancer cases.
Targeting a Key Enzyme That Fuels Cancer Growth
To test the new compound, researchers used a humanized mouse model of triple-negative breast cancer. The molecule SU212 attaches to an enzyme called enolase 1, or ENO1. This enzyme helps regulate glucose levels inside human cells and is produced in unusually high amounts by many cancer cells.
Once bound to ENO1, the molecule causes the enzyme to break down. This process ultimately reduced tumor growth and limited metastasis in the mice.
Under normal conditions, the enzyme plays a role in metabolism by helping cells convert glucose into energy. By disrupting this process in cancer cells, SU212 interferes with a critical pathway that tumors use to survive and spread.
Malhotra noted that this mechanism may be particularly relevant for patients who also have metabolic disorders such as diabetes, a chronic disease that leads to high blood sugar levels.
Potential for Treating Multiple Types of Cancer
The researchers believe that drugs targeting enolase 1 may have benefits beyond triple-negative breast cancer. Other cancers that are influenced by this enzyme include glioma, pancreatic cancer, and thyroid carcinoma.
“A drug that targets enolase 1 could help improve the treatment of these cancers too,” he said.
Malhotra joined OHSU in 2020 after working at Stanford University, where his laboratory continued studying the molecule. The compound was originally developed during his earlier research at the National Cancer Institute in Bethesda, Maryland.
As co-director of OHSU’s Center for Experimental Therapeutics, Malhotra works with colleagues to move laboratory discoveries toward clinical applications that can benefit patients treated in OHSU hospitals and clinics.
“There is definitely great science going on here, and we want to translate that science for the benefit of people,” he said.
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. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.