Gene that makes cells ‘sticky’ could be the key to stopping spread of breast cancer

The clinical statistics for breast cancer paint a remarkably accurate picture of where research has got to and where it is going in the future.  You only need to look at two timelines of events to see real life impact of the disease and the breakthroughs that have shaped it.

The amount of new breast cancer cases diagnosed each year has been steadily increasing since the mid 1970’s – a stark reflection of an ageing population (cancer is an ageing disease after all) and a product of routine screening.  There are currently around 50,000 new breast cancer cases diagnosed each year and this is predicted to rise to 57,000 by 2025.  Conversely, the amount of people dying from breast cancer has been steadily decreasing since the 1990’s, a direct result of early disease detection and development of effective treatments.  Deaths from breast cancer have dropped nearly 39% since the mid 1980’s, but can we expect this decline to continue?

An estimated 12,000 women die of breast cancer each year in the UK and most if not all of these deaths can be attributed to the secondary form of the disease.  This is also known as metastatic breast cancer, when tumour cells spread to other tissues of the body, set up shop and seed a secondary tumour.  A tumour in the breast tissue is not likely to be lethal but a tumour in the brain, lungs or liver tells a different story entirely.  In fact, breast cancers confined to the breast have cure rates that exceed 90%, whereas metastasis to the brain can reduce survival rates to below 20%.  A lack of treatment options and no specific drugs for metastatic breast cancer means that unless all breast cancers are prevented from progressing then death rates can’t fall into a continual decline.

It is for this reason that cancer charities and researchers are turning their attention to understanding the process of metastasis so that new treatments and preventative strategies can be developed.  Metastasis is a complex process involving genetic and molecular changes to tumour cells at different stages of progression.  These changes help the cells to migrate away from the primary tumour, recruit blood vessels to aid their spread, invade biological tissue at a secondary site and survive there long enough to develop a new tumour.  Because there may be tumour cells at various stages of metastasis at any one time, these changes also make it extremely difficult to treat.

Researchers from the Breakthrough Breast Cancer Research Centre, housed at the Institute of Cancer Research in London, are one team pitching in to find out how and why secondary breast cancer occurs and what can be done to stop it.  In a paper recently published in Cancer Discovery, Professor Clare Isacke and her team describe a new gene that promotes the formation of secondary breast cancer, and reveal a potential new treatment that could block it.

The team first silenced over 1000 genes in mammary tumour cells before implanting them into mice.  They then waited until secondary tumours formed in the lungs of the mice before collecting tumour samples and analysing the cancer genomes.  The theory was that tumour cells with certain genes switched off would set up home in the lungs, and by assessing the genetics of these tumours, the researchers hoped to identify specific genes that facilitate breast cancer metastasis.

One of the genes that they identified was of particular interest because of a known role it plays in enabling metastatic cancer cells to stick to secondary tissues and seed new tumours.  The gene in question, called ‘ST6GalNAc2’ codes for a protein that alters the characteristic features of the cell surface.  The outer surface of a cell is embedded with molecules that dot the landscape like mountains and forests on the Earth’s surface.  The ST6GalNAc2 protein chops off a specific molecule from the surface of the cell and as a result, the cell is no longer able to pick up a second molecule called ‘galectin-3’, which is present in the fluid surrounding our cells.  With the ST6GalNac2 gene switched off, the cancer cells pick up lots of galectin-3 and become more likely to stick to areas like the lungs.

The researchers suggest that that the ST6GalNac2 gene could be used as a marker to select patients with a particular type of breast cancer that would benefit from treatment with a drug that prevents galectin-3 from making the tumour cells ‘sticky’.  Clinical trials have already shown these drugs to be safe and could provide a new treatment option for the prevention of secondary disease.





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