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. Triple-negative breast cancer is a progressive disease for which there are currently few effective treatments.
In a study published in a journal cell report medicineThe research team describes how an experimental molecule called SU212 blocks an enzyme that plays a key role in cancer progression. The findings came from experiments using humanized mouse models designed to mimic human disease.
“This is an important advance in the treatment of triple-negative breast cancer,” said lead author Dr. Sanjay V. Malhotra, co-director of the Center for Experimental Therapies at the OHSU Knight Cancer Institute. “Triple-negative breast cancer is an aggressive cancer, and there are currently no effective treatments.”
The next stage of development includes moving this molecule into human clinical trials. This process requires significant resources to obtain Food and Drug Administration approval and begin studies in patients.
Malhotra, the Sheila Edwards Leenhart Endowed Chair in Cancer Research and professor of cell biology, developmental biology and cancer biology in the OHSU School of Medicine, said the same strategy could be used to treat other types of cancer.
Triple-negative breast cancer accounts for approximately 15% of all breast cancer cases.
Targets key enzymes that promote cancer growth
To test the new compound, the researchers used a humanized mouse model of triple-negative breast cancer. The molecule SU212 binds to an enzyme called enolase 1, or ENO1. This enzyme helps regulate glucose levels in human cells and is produced in abnormally large amounts by many cancer cells.
When bound to ENO1, this molecule causes the enzyme to degrade. This process ultimately reduced tumor growth and limited metastasis in the mice.
Under normal conditions, enzymes play a role in metabolism by helping cells convert glucose into energy. By interfering with this process in cancer cells, SU212 disrupts a critical pathway that tumors use to survive and spread.
Dr. Malhotra noted that this mechanism may be particularly relevant for patients suffering from metabolic disorders such as diabetes, a chronic disease that causes high blood sugar levels.
Possibility to treat multiple types of cancer
Researchers believe that drugs targeting enolase 1 may have benefits beyond triple-negative breast cancer. Other cancers affected by this enzyme include glioma, pancreatic cancer, and thyroid cancer.
“Drugs that target enolase 1 may also help improve treatment of these cancers,” he said.
Malhotra joined OHSU in 2020 after working at Stanford University and continuing to research molecules in the lab. The compound was originally developed during his early research at the National Cancer Institute in Bethesda, Maryland.
As co-director of OHSU’s Center for Experimental Therapeutics, Malhotra works with colleagues to advance laboratory discoveries into clinical applications that benefit patients treated at OHSU’s 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.
This research was supported by the National Institutes of Health’s National Cancer Institute, National Institute on Aging, and National Heart, Lung, and Blood Institute, award numbers N91019D00024, RF1AG079890, and R01HL164729. Department of Defense Award HT9425-23-1-0796. Knight Cancer Institute and OHSU’s Biomedical Innovation Program. and the Sheila Edwards Leenhart Endowment Fund. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.
