Improved radiotherapy for cancer patients could be around the corner. Researchers have identified a key piece in the puzzle of how tumours protect themselves from radiation, revealing how cancers could be made more vulnerable to treatment.

Around half of cancer patients are treated using radiotherapy, which involves blasting cancer cells with radiation either to remove the disease completely or prevent it spreading through the body. Depending on the type of cancer, success rates can vary almost all the way from zero to 100%. Overall, only about half of those who receive radiotherapy in the hope of a cure are actually cured.

This poor success rate is partly due to the fact that in the aftermath of radiation treatment, tumour cells produce molecules that protect their blood supply, says Mark Dewhirst of Duke University Medical Center in Durham, North Carolina. These compounds, called cytokines, promote the growth of new blood vessels to replace those killed by the radiation treatment.

To investigate how this happens, Dewhirst and his team measured the levels of a molecule called hypoxia inducible factor-1 (HIF-1) in mouse tumours treated with radiation. HIF-1 is known to stimulate the production of cytokines.

After radiation treatment, the tumours have higher levels of HIF-1 than before, the researchers report in the journal Cancer Cell¹. This in turn boosts cytokine production, protecting the tumour's blood supply from damage.

If production of the molecule could be reduced, the tumour's lifeline would be broken, making radiotherapy for humans more effective, Dewhirst hopes. "The obvious thing to do is go after HIF-1," he says.

The team have already succeeded in mice. When the researchers treated cancerous mice with a drug called YC-1, which blocks the production of HIF-1, subsequent radiation therapy was more effective at destroying blood vessels in tumours without harming normal vessels.

It is a potentially valuable step forward, according to James Oleson, a radiotherapy specialist also at Duke University Medical Center. Combining radiation therapy with drugs to weaken tumours' blood supply is an exciting idea, he says.

YC-1 has not yet been tested in humans. But another drug, 2-methoxyestradiol, has been shown to inhibit HIF-1 production in human cancer patients. The naturally occurring compound, produced under the trade name Panzem, can also kill cancer cells.

Such drugs should help to improve the hugely varying success rates of cancer treatment, Oleson hopes.

References

Moeller, B. J., Cao, Y., Li, C. Y. & Dewhirst, M. W. . Cancer Cell, 5, 429 - 441, (2004).

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