AI Summary
The article discusses research from Drexel's College of Medicine on new drugs showing promise in shrinking breast cancer brain metastases. Researchers identified drugs targeting a key metabolic enzyme in cancer cells in the brain, which led to shrinking tumors in a mouse model for the first time. The compounds AD-5584 and AD-8007 were found to effectively starve tumors of a key energy source by crossing the blood-brain barrier and blocking ACSS2 function. This discovery could lead to more effective therapies for breast cancer brain metastases.
Researchers from Drexel’s College of Medicine have identified new drugs that show early success in shrinking breast cancer tumors that have metastasized in the brain. The discovery marks the first time that targeting a key metabolic enzyme in cancer cells in the brain has shrunk tumors in a mouse model. The findings, which could develop into more effective therapies for breast cancer brain metastases, were recently published in the journal Frontiers in Pharmacology.
Brain tumor growth depends on converting an energy source for the brain known as acetate, to acetyl-CoA -; a molecule involved in biochemical reactions in carbohydrates, proteins and in metabolism and that aids in energy production -; using an enzyme known as acetyl-CoA synthetase 2, or ACSS2.
With this knowledge, the Drexel team used computer models to identify stable drug compounds that can break through the blood-brain barrier -; a major obstacle plaguing many existing drug options for cancer patients -; bind to ACSS2, block its function and shrink tumors in the brain.
Currently available inhibitors aren’t very good, or don’t get to the brain. This work is still in very early stages, but we’re finding that these novel compounds are crossing the blood-brain barrier and effectively starving tumors of a key energy source.”
Mauricio Reginato, PhD, senior author, professor and chair of the department of Biochemistry & Molecular Biology in the College of Medicine
In the lab, the compounds, known as AD-5584 and AD-8007, selectively killed cancer cells and blocked tumor growth in animal models, as well as reduced