Richard G. Petty, MD

Breast Cancer and the Gang of Four

People of a certain age will remember the ominous "Gang of Four" who were primarily blamed for the events of the Cultural Revolution in China.

Now new research published in the journal Nature has exposed an equally ominous "Gang of Four," but this time it is a set of four genes is responsible for the lethal spread of breast cancer.

A team in New York with researchers now working at the Hospital Clinic de Barcelona and the Institute for Research in Biomedecine in Spain, has identified four key genes in human breast cancer cells that play a role in metastasis, or the spread of the cancer, to the lungs.

A number of genes are already known to contribute to the spread to the lungs. But Prof Joan Massagué and colleagues at Memorial Sloan Kettering Cancer Centre, New York, now show how four co-operate to promote the formation of new tumour blood vessels, the release of cancer cells into the bloodstream, and the penetration of tumour cells from the bloodstream into the lung.

The gene set comprises EREG, MMP1, MMP2 and cyclooxygenase (COX2). (That is the same COX2 that you will have heard about as a target for some arthritis and anti-inflammatory medicines. It is the abnormal activation of all four that enables the breast cancer to invade the lungs. Although shutting off these genes individually can slow cancer growth and metastasis, the researchers found that turning off all four had a dramatic effect.

Prof Massagué said:

"The remarkable thing was that while silencing these genes individually was effective, silencing the quartet nearly completely eliminated tumour growth and spread."

In experiments on human breast tumours implanted in mice, the researchers also found that they could reduce the growth and spread of the disease by simultaneously targeting two of the proteins produced by these genes, using drugs already on the market.

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

The researchers now want to test combination therapy with the drugs – cetuximab (Erbitux) and celecoxib (Celebrex) – to treat breast cancer metastasis.

The other two genes are matrix metalloproteinases (MMP1 and MMP2) that are involved in the formation of new blood vessels.

A second study, also published in Nature, reports that investigators in Texas have isolated 87 genes that seem to affect how sensitive human cancer cells are to certain chemotherapy drugs.

The study highlights a new way to screen for alterations in cancer cells that make them specifically sensitive to treatments, so that they may leave normal tissue relatively unharmed.

This is important work that unlocks  another piece of the mystery of at least one type of cancer.

It will not be the whole story: we still need to find out why tumors can spread to other organs and how environmental factors, including states of mind, may have an impact on the spread of tumors.

And it is yet more evidence that inflammation is one aspect of the spread of tumors.

About Richard G. Petty, MD
Dr. Richard G. Petty, MD is a world-renowned authority on the brain, and his revolutionary work on human energy systems has been acclaimed around the globe. He is also an accredited specialist in internal and metabolic medicine, endocrinology, psychiatry, acupuncture and homeopathy. He has been an innovator and leader of the human potential movement for over thirty years and is also an active researcher, teacher, writer, professional speaker and broadcaster. He is the author of five books, including the groundbreaking and best selling CD series Healing, Meaning and Purpose. He has taught in over 45 countries and 48 states in the last ten years, but spends as much time as possible on his horse farm in Georgia.

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