New molecule offers a promising avenue to treat triple-negative breast cancer

A new molecule developed by researchers at Oregon Health & Science University offers a promising avenue to treat intractable cases of triple-negative breast cancer - a form of cancer that is notoriously aggressive and lacks effective treatments.

In a study published today in the journal Cell Reports Medicine, researchers describe the effect of a molecule known as SU212 to inhibit an enzyme that is critical to cancer progression. The research was conducted in a humanized mouse model.

It's an important step forward to treat triple-negative breast cancer. Triple-negative breast cancer is an aggressive form of cancer and there are no effective drugs available right now."

Sanjay V. Malhotra, Ph.D., senior author, co-director of the Center for Experimental Therapeutics, OHSU Knight Cancer Institute

The next step in developing a treatment involves advancing the molecule toward a clinical trial for people, a process that requires a substantial investment of resources to garner Food and Drug Administration approval and to initiate clinical trials.

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.

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.