Gene 'switch' that helps breast cancer spread identified

London: Scientists have identified a genetic 'switch' that helps breast cancer spread through the body, an advance that may help combat the deadly disease.

The team from Imperial College London and The Institute of Cancer Research in London showed that the 'switch' boosts the production of a type of internal scaffolding. This scaffolding is a type of protein, called Keratin-80, and related to the protein that helps keep hair strong. Boosting the amount of this scaffolding makes the cancer cells more rigid, which the researchers say may help the cells clump together and travel in the bloodstream to other parts of the body. The researchers, who published their work in the journal Nature Communications, studied human breast cancer cells treated with a common type of breast cancer drug called aromatase inhibitors.

The team found the same switch is involved in breast cancer cells becoming resistant to the medication (meaning the drugs are no longer effective if the cancer returns). Targeting this switch with a different drug could help reverse this resistance, and make cancer less likely to spread, said Luca Magnani, lead author of the research at Imperial. "Aromatase inhibitors are effective at killing cancer cells, but within a decade post-surgery around 30 per cent of patients will relapse and see their cancer return -- usually because the cancer cells have adapted to the drug," said Magnani. "Even worse, when the cancer comes back it has usually spread around the body -- which is difficult to treat," he said.

The study suggests a type of genetic switch -- called a transcrip tion factor -- can turn on genes that cause the cancer cells to not only become resistant to the treatment, but move into health tissue around the body. "This research now needs to be followed up with larger studies, but if confirmed, targeting this genetic switch could prevent cancer cells from becoming resistant to the drugs, and from spreading to other areas of the body," said Magnani. Aromatase inhibitors are used to treat a type of breast cancer called oestrogen-receptor positive. These make up over 70 per cent of all breast cancers, and are fuelled by the hormone oestrogen. However, around 30 per cent of breast cancer patients taking aromatase inhibitors see their cancer eventually return.

This returning cancer is usually metastatic, meaning it has spread around the body, and the tumours are often now resistant to aromatase inhibitors. In previous research, the team discovered that when aromatase inhibitors starve cancer cells of oestrogen, some cells adapt by increasing production of cholesterol, which they then use for energy to survive. This means that if the cancer returns, it can no longer be killed by the same type of drugs.

In the latest research, which used human breast cancer cell cultures in the laboratory, the team found the switch that turns on genes that increase cholesterol production also activates genes that make the cells more rigid and prone to invade nearby tissues. The team also found that in women whose cancers had spread around the body, the cells contained higher amounts of Keratin-80. The team said larger scale patient studies are now needed to confirm the findings, but the research could provide new avenues for helping treat breast cancer that returns and spreads around the body.