US scientists have demonstrated a way to stop breast cancer spreading to other parts of the body by either switching off the genes involved or blocking them with drugs.
The study is published in the journal Nature.
Tumours formed from cancer that has spread or metastased from the primary site to other parts of the body cause 90 per cent of cancer deaths.
The process of metastasis or cancer spread is still much of a mystery to scientists. They can’t tell the difference between a tumour that won’t spread and one that will. And why, when hundreds of tumour cells get into the bloodstream every day, do only a small number of them take up residence in a new site and start multiplying?
Dr Joan Massagué from the Memorial Sloan-Kettering Cancer Center in New York, US, has been working in this field for some time. He and his team have been looking at cell regulation and how it helps cancer cells to spread to specific tissues.
In 2005, they found a number of genes that help breast cancer to metastase to the lungs. In this new study, they have identified four genes in particular that work together to help cells from the primary site to settle at a new site and grow.
The four genes are: EREG, MMP1, MMP2 and COX2.
Dr Massagué and his team performed two types of experiment. In one they switched off the genes, and in another they targeted them with drugs.
In the first experiment they took human breast cancer cells and switched off all four genes before inserting them into mice. The tumours did not grow, and metastasis to the lungs was greatly reduced.
However, when they only silenced the genes individually, the effect was nowhere near as dramatic.
In the second experiment they used a combination of three drugs to inhibit the action of the genes. Two of the drugs have already been approved for clinical use: cetuximab and celecoxib, while the third, GM6001, is still experimental.
The drugs had a similar effect to switching the genes off. And the two approved drugs without the experimental one also stopped the cancer from spreading.
In speculating on the results, the team suggested the four genes have to work together to help both tumour growth and spread.
They said the genes probably hijack blood vessels and make them feed the tumour instead of healthy cells. Then they help tumour cells get into the bloodstream, penetrate capillary walls in the lungs, become established, and start multiplying.
So far Dr Massagué and his team have been working with mice; they hope to set up trials with humans very soon. Since two of the drugs are already approved for clinical use, this should speed things up.
“You couldn’t have it better,” said Dr Massagué. However, other scientists would prefer to wait for the results of human trials before getting too excited.
The next stage, said Dr Massagué, is to find women whose breast cancer relies on these four genes. Then they can test whether the drugs they used with the mice will stop the metastasis to the lungs in humans.
This study makes a significant contribution to the theory of cancer metastasis. Many scientists believe that cancer spread starts after the primary tumour has reached maturity. But this research challenges that and suggests that cancer cells start migrating to other sites from the start. And the same genes that drive the growth of the primary tumour also help the cells to move and settle somewhere else.
Another potential contribution this study makes is the possibility that these same genes are involved in fuelling metastasis of other cancers, or at least that similar rules are involved. That is the hope expressed by Christoph Klein, who studies metastasis at the University of Regensburg in Germany.
While this study sheds valuable light on the mystery of metastasis, there are still areas that puzzle experts. For instance, some patients are diagnosed with metastased tumours without the primary tumour every being found. And nobody knows why different cancers spread to particular tissues, such as why breast cancer travels to lung and bone in particular.
“Mediators of vascular remodelling co-opted for sequential steps in lung metastasis.”
Gaorav P. Gupta, Don X. Nguyen, Anne C. Chiang, Paula D. Bos, Juliet Y. Kim, Cristina Nadal, Roger R. Gomis, Katia Manova-Todorova, Joan Massagué.
Nature 446, 765-770 (12 April 2007)
doi:10.1038/nature05760
Written by: Catharine Paddock
Writer: Medical News Today