A potential breakthrough in halting breast cancer metastasis has been announced by Israeli and American scientists, in mice. Whether the combination chemotherapy and genetic therapy works as well in men remains to be seen.
One in eight women worldwide are diagnosed with the disease every year, and the chance of dying from it, for women, is about 1 in 36. It's rarer in men but they should be tested, and if they get it, they're more likely to die than women are: the five-year survival rate for women overall was 83%, compared to 74% for men. So in contrast to the popular wisdom, finding a way to stop it from spreading matters to both sexes.
"We wanted to find a way to stop metastasis from happening altogether. It’s the turning point, where survival rates drop exponentially," said Dr. Noam Shomron of TAU's Sackler School of Medicine.
The mission, Shomron explains, is to thwart a cancer cell's ability to change shape and move, which is how metastasis happens. "Cancer cells alter their cytoskeleton structure in order to squeeze past other cells, enter blood vessels and ride along to their next stop: the lungs, the brain or other vital organs," he explains.
It had already been generally known that regulation of gene expression, by microRNAs, is key to malignant spread. The first step was to identify which specific genes are associated with metastasis.
The scientists began by studying all known mutations in breast tumors, and chose to work with mutations that other scientists had ignored, because they don't cause any change in proteins. They were mutations of regulatory sequences – in the parts of the DNA that control gene expression.
The scientists did find that mutations in regulatory sequences are involved in metastasis, Shomron explains.
In other words, by monkeying with these regulatory genes, perhaps they could stop metastasis, the scientists deduced. One way to monkey with genes is using microRNA, which are short sequences of RNA, that occur naturally. (They are coded by DNA of course but are not involved in protein expression, only in regulation.)
"MicroRNAs, gene expression master regulators, constitute an attractive candidate to control metastasis," wrote the team from Tel Aviv University and MIT.
Working with cells grown in vitro (in glass, before working with mice), the scientists found that applying their engineered microRNAs decreased the expression of a protein called Palladin, which is key to metastasis.
Onto the mice: First cancer was induced. Then the main tumor was cut out. Three weeks after that, the mice were evaluated. Mice treated with two of the tested microRNAs had very few or no metastatic sites, but the control group, injected with random scrambled RNAs, exhibited a fatal proliferation of metastatic sites, the team reported.
How likely is this mouse model to work on women, or men? "We realized we had stopped breast cancer metastasis in a mouse model, and that these results might be applicable to humans," said Dr. Shomron. "There is a strong correlation between the effect on the genes in mouse cells and the effect on the genes in human cells. Our results are especially encouraging because they have been repeated several times at TAU and at MIT by independent groups."
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