Cancer's "Master Switch"

There's a "master switch" that cancer cells use to dispatch protective messages to nearby blood vessels, fortifying the vessels against deadly onslaughts of radiation. The messages enable blood vessels to survive and ultimately nourish any remaining cancer cells that escape toxic radiation therapy. These findings by researchers at Duke were published in the May 2004 issue of Cancer Cell.

Radiation biologists from the Comprehensive Cancer Center identified the master switch as a protein called "Hypoxia Inducible Factor" (HIF-1) that turns on production of these protective messages. With radiation therapy and experimental drugs, they suppressed HIF-1 in animals with cancer, successfully inhibiting blood-vessel growth and, thereby, the tumors they nourish. The Duke scientists hope to test this potential new combination therapy in humans in the near future.

The Duke discovery follows dozens of recent developments in the field of anti-angiogenesis, in which scientists have attempted to block specific proteins that give rise to or protect tumor-feeding blood vessels. The most noteworthy success has been Avastin, the first drug to be approved by the FDA to suppress angiogenesis in patients with spreading colorectal cancer. Avastin inhibits the protein VEGF and has been shown to extend patients' lives when taken together with chemotherapy.

Principal investigator Mark Dewhirst, professor of radiation oncology at the medical center, and first author Benjamin Moeller, a graduate student in the Duke M.D./Ph.D. program, say their technique of suppressing HIF-1 expression could, theoretically, be a more potent inhibitor of blood vessel survival than the current approach of just suppressing a single protein, such as VEGF.

Approximately half of all cancer patients in the U.S. are treated with radiation therapy. However, the success of the therapy depends largely on how sensitive a tumor's blood vessels are to radiation. If blood vessels in the tumor survive after radiation, they can provide nutrients to the surviving cancer cells to begin rebuilding the tumor. Thus, knowing how HIF-1 works inside cancer cells is critical to manipulating its behavior and making blood vessels more responsive to radiation.