Metastasis-causing genes identified in breast cancer

Researchers at the Memorial Sloan-Kettering Cancer Center (MSKCC) in the US have identified genes which work together to aid the spread of breast cancer tumours to the lungs in animal studies.

Dr Joan Massague, a Howard Hughes Medical Institute investigator at MSKCC and her colleagues identified four genes which cooperate to help cancer spread throughout the body, including one affected by arthritis drugs.

Massague's team suppressed each gene individually and found while silencing these genes individually was effective, silencing the whole group almost eliminated tumour growth and spread. The genes are called EREG, MMP-1, MMP-2 and COX-2.

The researchers injected cells without the four genes directly into mice. When the cancer cells reached the lung capillaries, they lodged there, suggesting that the cells use the four genes to break through the walls of lung capillaries and start growing.

Previous research has revealed that people who use drugs that affect COX-2, including aspirin, ibuprofen and the COX-2 inhibitor Celebrex (celecoxib), have a lower risk of some cancers.

Massague tested the role of Celebrex and cancer drug Erbitux (cetuximab), which is manufactured by Imclone Systems and Bristol-Myers Squibb, in the suppression of the action of two of the four genes.

Elsewhere, scientists at the University of Texas Southwestern Medical Center in Dallas screened the whole human genome to find the genes responsible for making lung tumour cells vulnerable to the cancer drug paclitaxel. They found that a total of 87 different genes work in combination to help make cancer more vulnerable to drug treatment.

When the researchers turned these genes off, they could kill cancer cells with Taxol (paclitaxel) at doses 1,000 times lower than normally given to patients. Some of the genes are already targeted by current cancer drugs and others form the basis of experimental cancer vaccines currently in development.

The study results go some way to explaining why chemotherapy agents are less effective in treating some cancers, especially lung cancer, as well as offering a route of treatment involving less toxic doses.

Both studies were published in last weekís issue of the journal, Nature, and could aid in the development of more effective drugs to combat cancer. Cancer is generally treatable before it has metastasised, but once tumours spread from their initial location, they become difficult to destroy.

The global market for cancer treatment has just seen a period of rapid growth and according to IMS figures will soon exceed the value of cardiovascular drugs, which is currently the largest therapy area.

According to Steven Seget of Delphi Pharma, between 2003 and 2005, global sales for cancer treating drugs increased 40 per cent and now account for more than eight per cent of total global pharmaceutical sales. Seget added that although growth rates for the cancer market will slow due to generic competition, he predicts an expansion to USD 85.3bn (EUR 62.8bn/ GBP 42.5bn) by 2010, which is equivalent to CAGR of 11.1 per cent.