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Genes That Spread Breast Cancer to Lungs

Armen Hareyan's picture

Cancer Genes

Cancer researchers have identified a set of genes they say promote the spread of breast tumors to the lungs. The finding helps explains the steps by which breast cancer cells invade the lungs and suggests biological targets for existing drugs to stop the process. VOA's David McAlary reports.

Most cancer deaths are caused by the spread of tumor cells to other organs, a process called metastasis. Breast cancer spreads mainly to the lungs, the liver, and the bones, as in the case of the wife of U.S. Democratic Party presidential candidate John Edwards.

A new study of human breast cancer cells implanted in mice shows that metastasis to the lungs depends on the abnormal activation of four genes working in concert. The study, published in the journal Nature, reveals that shutting off the genes individually can slow the growth and spread of breast cancer to the lungs, but turning off all four together almost completely stops the process - at least in mice.

The work was led by researchers at Memorial Sloan-Kettering Cancer Center in New York City, including microbiologist Don Nguyen.

"The four genes that we find here are not necessarily important for the early stages of tumor formation, but we predict that they are important for the stages at which a cancer becomes more aggressive and also metastasizes to other sites," said Don Nguyen.

The genes were already well known to cancer researchers before this study. One is essential for the growth and progression of several cancer types. Two others support the growth of blood vessels that feed tumors. The fourth has been previously implicated in promoting metastasis.

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The new research suggests that they work together at every step of the metastatic process to allow a breast tumor to develop blood vessels, let tumor cells pass through the vessel walls into circulation to the lungs, and finally permit them to pass out of the vessels there and resume growth.

Microscopic analysis of the mouse tumors showed that blocking all four genes greatly reduced the tangle of blood vessels. Microbiologist Nguyen says the vessels that did form allowed fewer cancer cells to escape into circulation.

"That is our prediction - that these genes can act at different stages of the metastatic process and that by blocking them, we can essentially stunt the tumor cells wherever they are, which would prevent them from getting to other organs," he said.

Two drugs already on the market act directly against proteins produced by the genes the study identifies. The researchers found that their combined use was more effective than each drug used alone.

"Cancer depends on the activity of many genes and so this finding confirms the clinical strategies that are designed today to do combination therapy, which is predicted to be much more effective at inhibiting the activity of multiple gene targets," said Nguyen.

The four genes are among 18 that the Sloan-Kettering team identified in earlier work as associated with breast cancer metastasis. The scientists are exploring the function of all of them in more detail, including whether they promote the cancer's spread to other organs.

Nguyen says they are also helping Sloan-Kettering physicians design clinical trials to see if the drugs they used in the mice can stymie a tumor's spread to human lungs.

"It is certainly promising that using therapies already available and that have been approved for safety, we can inhibit the activity of these genes," he said.