By combining gene therapy with chemotherapy and delivering it to a primary tumor site, researchers at Tel Aviv University’s Sackler Faculty of Medicine have discovered in mice an “extremely effective way” to prevent the spread of breast cancer to other parts of the body.
One in eight women worldwide contract breast cancer, making it the second leading cause of cancer death in women. The chance that any woman will die from breast cancer is about one in 36. About 80% of women with metastatic cancer die from the disease within five years of being diagnosed.
“The situation is bleak. Death rates from breast cancer remain high and relatively unchanged despite advances in medicine and technology,” said Noam Shomron, the research team’s leader. Survival has increased by only three percent in the last 20 years, he added. “We wanted to find a way to stop metastasis from happening altogether. It’s the turning point, where survival rates drop exponentially. Our mission was to block a cancer cell’s ability to change shape and move.”
Shomrom and his team published their findings in the peer-reviewed, open-access journal, Nature Communications
. The article describes how they harnessed the targeted delivery of microRNAs, small, non-coding RNA molecules found in plants, animals and some viruses, that regulate gene expression and RNA silencing.
Their research led to success in dealing with primary tumors in mice and blocking the movement of cancer to other sites in the mice’s bodies.
The TAU researchers based their approach on the 3Ds: database, drugs and delivery. They began by exploring bioinformatics databases to investigate the span of mutations in a tumor and identify precisely which ones to target. The scientists then procured a naturally occurring, RNA-based drug to control cell movement and created a safe nanovehicle with which to deliver the microRNA to the tumor site.
Two weeks after initiating cancer in the breasts of their mice, the researchers injected primary tumor sites with a hydrogel that contained naturally occurring RNAs to target the movement of cancer cells from primary to secondary sites.
Two days after the treatment, the primary breast tumors were gone.
Three weeks later the mice were evaluated with CT imaging, fluorescent labeling, biopsies and pathology. The researchers discovered that the mice treated with two different microRNAs had very few or no metastatic sites, whereas the control group – injected with random scrambled RNAs – exhibited a fatal proliferation of metastatic sites.
“We realized we had stopped breast cancer metastasis in a mouse model, and that these results could be applicable to humans,” Shomron said. “There is a strong correlation between the effect on genes in mouse cells and the effect on those in human cells. Our results are especially encouraging because they have been repeated several times at TAU and at the Massachusetts Institute of Technology by independent groups.”
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