Johns Hopkins researchers say they have uncovered the path that breast cancer takes to the lungs, information that could lead to therapies to block metastases responsible for 90 percent of breast cancer deaths.

"Metastasis transforms breast cancer from a local, curable disease, to one that is systemic and lethal," said Dr. Gregg L. Semenza, director of the Vascular Program in the Institute for Cell Engineering. "Metastasis was long thought a late event in cancer progression, but we have now shown metastasis to be an early event that is dependent on HIF-1."

The HIF-1 protein, which Semenza and a team discovered two decades ago, controls the genes that enable cells to survive in tumors where there is low oxygen. Other research has shown increased HIF-1 activity results in lower survival rates in those with breast cancer.

The findings were published in the Sept. 12 issue of the Proceedings of the National Academy of Science Early Edition and in the Aug. 22 issue of Oncogene.

Researchers focused on the lung to trace the role HIF-1 plays in breast cancer metastasis. They found the protein enabled breast cancer cells to produce enzymes that prepare the lung for cancer to spread. They also play a role in helping cancer cells travel to the lungs through blood vessels.

Semenza and researchers also found that a medication used to treat irregular heartbeats can block HIF-1 production and can stop liver and prostate cancer cells from growing. They studied if digi-talis can do the same with metastatic breast cancer and in mice, there were fewer and smaller tumors in the lungs. Clinical trials could be next.