Scientists at Boston Children’s Hospital have discovered a hidden nuclear role for the metabolic enzyme FAH that helps breast cancer cells resist treatment — a finding that could open new paths against drug resistance.

The study, published in Science Advances by researchers Kanarek and Muranen, found FAH inside the nucleus of hormone-receptor-positive (HR+) breast cancer cells treated with CDK4/6 inhibitors, a widely used class of targeted therapy. There, the enzyme activates CDK9, a protein that helps cancer cells survive the drugs.

Crucially, blocking CDK9 reversed the resistance in laboratory experiments, suggesting a new combination strategy: pairing CDK4/6 inhibitors with CDK9 blockers to keep tumours responding to treatment.

The discovery also positions FAH as a potential biomarker — measuring its nuclear presence could one day help doctors predict which patients are likely to stop responding to CDK4/6 inhibitors and need a different approach.

HR+ breast cancer is the most common subtype of the disease, and resistance to CDK4/6 inhibitors is one of oncology’s biggest challenges. The team says clinical studies will be needed to confirm whether targeting this pathway helps patients.