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09/27/1999 07:00:00

A heart medication is found effectivein treating skin cancer, Caltech researchers discover

PASADENA-Researchers have discovered that one type of drug used for human heart disease can inhibit the growth of skin cancer cells.

The drug, known as BQ788, is proving effective in suppressing skin cancer in mice, and drugs of this type could have potential for ovarian and prostate tumors as well. In the September 28, 1999, issue of the Proceedings of the National Academy of Sciences, California Institute of Technology biology professor Paul Patterson and researchers Ronit Lahav and Garrett Heffner report that the drug can stop melanoma tumor growth and even reduce tumors in some cases.

Further, the drug seems to be effective both as a direct treatment of the tumor and when injected systemically into the animal. The latter result is particularly promising as it has the potential for also suppressing metastasis, or the spread of tumors to other organs, says Patterson.

"If you went to the doctor with a tumor on the skin, he would take it out immediately," says Patterson, who is executive officer for the Division of Biology at Caltech. "So the first line of treatment is to surgically excise the tumor, and if it's a superficial tumor, you essentially have a complete cure.

"But the worry is when the tumor has penetrated more deeply and already metastasized," he says. "We think this drug could turn out to be an effective way to stop cancer cells from spreading, or at least stop their growth if they have already spread."

The strategy is based on the targeting of "growth factors," or proteins that cells use to stimulate their growth. The cancerous state represents a reversal of healthy, mature cells to a state similar to that of embryonic cells. In other words, cancerous cells tend to multiply rapidly, just as cells do in a developing embryo.

Lahav, the lead author on the paper, reasoned that melanoma cancer cells perhaps use a growth factor similar to that employed by their precursor cells in the embryo. She showed that such a growth factor, called endothelin, acts on the embryonic cells, and is also made by the cancer cells. By serendipity, the heart drug BQ788 is an antagonist for the endothelin receptor B. Thus, BQ788 is a substance that disrupts the receptor from performing its function in the cell.

Lahav found that this drug can stop human melanoma cell growth when introduced into cell cultures. In fact, the drug not only makes the cells stop dividing, but it can also kill such cells.

When the drug was given to mice with tumors, tumor growth slowed dramatically, and in some cases even regressed.

"It works whether you inject it into the tumor or into the body cavity," Patterson says. "In about half the mice, the tumors actually shrank."

Patterson says there is reason to think this type of drug could also work on certain other cancers (ovarian, prostate) where runaway cell growth may also be controlled by the same growth factor, endothelin.

Ronit Lahav is a postdoctoral scholar from Israel, and Garrett Heffner is a Caltech sophomore who participated in this research the summer after graduating from high school.

Written by Robert Tindol