Key to breast cancer spread found


Apr 11, 2007

Scientists have come closer to working out what makes breast cancer deadly.

Four genes have been found to work together to drive the spread of breast cancer to the lungs.

Turning off all four genes at once dramatically reduces the ability of breast tumours to spread - or metastasise - a study in mice showed.

Reporting the results in Nature, the US team said they were planning clinical trials of drugs known to target two of the genes in the set.

Tumours spread when cancer cells break away and travel through the bloodstream to a different site in the body - a process called metastasis.

It is the ability to spread to other tissues and organs that makes cancer potentially deadly and metastases are very common in the late stages of cancer.

In a series of experiments, Dr Massague found that four of those genes which produce proteins which combine to enable cancer cells to escape into the bloodstream and get into the lungs.

Knocking out each of the genes individually in human cancer cells that had been implanted in mice had a small effect on cancer growth and metastasis.

But turning off all four genes at once almost eliminated tumour growth and spread, and the tangle of blood vessels that is normally seen in a tumour was greatly reduced.

Injecting cancer cells that had all four genes turned off into the bloodstream of mice also showed that the cells lacked the ability to get into lung tissue.


Two drugs known to inhibit two of the proteins produced by the genes - cetuximab and celecoxib - were also shown to reduce the growth and spread of the breast tumours in mice if used in combination.

Discussions are underway for clinical trials in humans.

Dr Massague, chair of the cancer biology and genetics programme at Memorial Sloan-Kettering Cancer Center said: "We found that the combination of these inhibitory drugs was effective even though the drugs individually were not very effective.

"This really nailed the case that if we can inactivate these genes in concert, it will affect metastasis."

"These genes are used together to attract blood vessels and enter the blood stream and then once they reach the lung they use the same strategy to enter the lungs."

Cancer spread

Dr Massague is also looking at which genes promote metastasis to other sites in the body, such as brain and bone and whether the same or similar genes are involved in cancer spread in other cancer types, such as colon cancer.

Dr Anthea Martin, cancer information officer at Cancer Research UK, said: "Cancer's ability to spread around the body can make the disease difficult to treat.

"This research has added to our knowledge of the genes that may be involved in the spread of breast cancer to the lungs.

"The more we understand about this process, the more likely it is that scientists will be able to design treatments to prevent it from happening.

"It is not known if the same genes are involved in the spread of all cancers, but this work is a great starting point for scientists looking at this important area of research."