Preclinical study shows early activity of enolase inhibitors in cancer cells with genetic loss of ENO1
Researchers at The University of Texas MD Anderson Cancer Center have developed a novel targeted therapy, called POMHEX, which blocks critical metabolic pathways in cancer cells with specific genetic defects. Preclinical studies found the small-molecule enolase inhibitor to be effective in killing brain cancer cells that were missing ENO1, one of two genes encoding the enolase enzyme.
The study results provide proof of principle for a treatment strategy known as collateral lethality, in which an important protein is lost through genetic deletion as a bystander near a tumor suppressor gene, and a redundant protein is blocked therapeutically.
“Collateral lethality could expand the scope of precision oncology beyond activated oncogenes, and allow targeting of genomic deletions, largely considered un-actionable,” said corresponding author Florian Muller, Ph.D., assistant professor of Cancer Systems Imaging and Neuro-Oncology. “Our work provides proof of principle that this approach can actually work with a drug in animal models.”
