Triple-negative breast cancer (TNBC) is aggressive and hard to treat because it resists many therapies. Researchers have found a way to corner it — a “one-two punch” that forces the cancer cells to kill themselves.
Scientists at the Medical University of South Carolina Hollings Cancer Center, led by Dr. Ozgur Sahin, found that blocking an enzyme called LOX (lysyl oxidase) weakens TNBC cells and forces them onto a backup survival pathway controlled by a protein called DHODH. Block that too, and the cells undergo ferroptosis — a lethal, iron-dependent form of cell death. The team paired an experimental LOX inhibitor with leflunomide, an already FDA-approved drug that blocks DHODH. The work appeared in Cell Reports Medicine.
What it did
Across multiple patient-derived tumor models — including chemotherapy-resistant ones — the combination significantly blocked tumor growth, and it outperformed the LOX inhibitor plus standard chemotherapy, without major weight loss or kidney/liver toxicity. “First, we block LOX, which weakens the cancer cells…we deliver the second punch by blocking that pathway, too,” Sahin said.
Why it matters — and the caveat
Using an approved drug (leflunomide) as one half of the combination could speed translation. But this is preclinical research in lab and patient-derived models; the researchers hope to complete human safety testing within a few years. Still, a strategy that exploits cancer’s own resistance mechanism — turning its backup plan into a vulnerability — is a compelling approach for a subtype with few targeted options.