There is an urgent need for novel treatments for breast cancer brain metastasis, which can kill within months.

Professor Mauricio Reginato, his colleagues and student researchers have made promising discoveries involving the enzyme acetyl-CoA synthetase 2 (ACSS2). This enzyme converts acetate into acetyl-CoA, a source of energy for brain tumors because most sugar in the human body is consumed by the brain.

“Tumor cells use the sugar glucose as a source for fuel,” Reginato explains. “But in the brain, they’re outcompeted, so they have to use other metabolic sources, like glutamine or acetate.”

The team was trying to target ACSS2 to prevent tumor growth, when they saw that it was not only stopping the growth but also causing cell death.

They successfully validated their results genetically in brain tumors and reported findings in Oncogene in 2022.

Reginato ultimately hopes to block tumor cells with drugs targeting ACSS2, by elevating proteins that kill off cancer cells.

He and colleagues have developed compounds that can cross the blood-brain barrier while targeting ACSS2 and are currently testing whether these new drugs will work synergistically with current treatments such as radiation or FDA-approved drugs.