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Genes may gang up to help tumors spread

Four genes gang up together to help cancer spread throughout the body, including one affected by arthritis drugs, researchers said Wednesday.
/ Source: Reuters

Four genes gang up together to help cancer spread throughout the body, including one affected by arthritis drugs, researchers said Wednesday.

And a second study found that 87 different genes work to help make cancer more vulnerable to drug treatment.

Both studies published in this week’s issue of the journal Nature should help scientists develop more effective drugs to fight cancer, the second-leading cause of death in the developed world.

Cancer is highly treatable before it has spread. But once tumors break out of their initial spot in a process called metastasis, they are almost impossible to suppress for long.

Dr. Joan Massague, a Howard Hughes Medical Institute investigator at the Memorial Sloan-Kettering Cancer Center in New York, and colleagues identified four genes that worked together to help breast cancer tumors spread to the lungs of mice.

The genes are called EREG, MMP-1, MMP-2 and Cox-2.

Massague’s team suppressed each gene one by one and found a small effect. “The remarkable thing was that while silencing these genes individually was effective, silencing the quartet nearly completely eliminated tumor growth and spread,” Massague said in a statement.

Further experiments showed just what the genes do to help the tumors spread.

The researchers injected cells lacking the four genes directly into mice. “When these cells reached the lung capillaries, they just got stuck there,” Massague said.

It appears that the cells use the four genes to break apart the walls of lung capillaries, get inside and start growing.

Researchers have already noticed that people who use drugs that affect Cox-2, including aspirin, ibuprofen and the Cox-2 inhibitor Celebrex, have a lower risk of some cancers.

Combination therapy
Celebrex, made under the chemical name celecoxib by Pfizer, and a cancer drug named Erbitux, made by Imclone Systems Inc. and Bristol-Myers Squibb Co. under the chemical name cetuximab, work against two of the four genes.

Massague’s team tested them together in the mice.

“We found that the combination of these two inhibitory drugs was effective, even though the drugs individually were not very effective,” said Massague. “This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis.”

A second team of researchers identified 87 different genes that, when turned down, helped certain chemotherapy drugs destroy tumors.

Michael White and colleagues at the University of Texas Southwestern Medical Center in Dallas screened practically the whole human genome to find the genes responsible for making lung tumor cells vulnerable to the cancer drug paclitaxel.

When they turned these genes down, they could kill cancer cells with paclitaxel, also known as Taxol, at doses 1,000 times lower than normally used.

Some of the genes are already targeted by current cancer drugs, they said, and others are the basis of experimental cancer vaccines.

Their findings may help explain why some chemotherapy agents work so poorly against some cancers, notably lung cancer. And it could help doctors use the highly toxic drugs at lower doses.

“Chemotherapy is a very blunt instrument,” White said in a statement. “It makes people sick, and its effects are very inconsistent. Identifying genes that make chemotherapy drugs more potent at lower doses is a first step toward alleviating these effects in patients.”