New gene therapy technique may prevent cancer spread

MIT scientists have developed a new gene therapy technique that can stop the spread of malignant cells around the body - the leading cause of mortality in women with breast cancer.
The treatment uses microRNAs - small noncoding RNA molecules that regulate gene expression - to control the spread of cancer cells around the body, known as metastasis.
The therapy could be used alongside chemotherapy to treat early-stage breast cancer tumours before they spread, according to Natalie Artzi, a principal research scientist at Massachusetts Institute of Technology (MIT) in the US.
"The idea is that if the cancer is diagnosed early enough, then in addition to treating the primary tumour (with chemotherapy), one could also treat with specific microRNAs, in order to prevent the spread of cancer cells that cause metastasis," Artzi said.

The regulation of gene expression by microRNAs is known to be important in preventing the spread of cancer cells.
Recent studies have shown that disruption of this regulation, for example by genetic variants known as single nucleotide polymorphisms (SNPs), can impact gene expression levels and lead to an increase in the risk of cancer.

To identify the specific microRNAs that play a role in breast cancer progression and could therefore potentially be used to suppress metastasis, the research teams first carried out an extensive bioinformatics analysis.
They compared three datasets: one for known SNPs; a second for sites at which microRNAs bind to the genome; and a third for breast cancer-related genes known to be associated with the movement of cells.

This analysis showed a variant, or SNP, known as rs1071738, which influences metastasis. They found that this SNP disrupts binding of two microRNAs, miR-96 and miR-182.
This disruption in turn prevents the two microRNAs from controlling the expression of a protein called Palladin.
Previous research has shown that Palladin plays a key role in the migration of breast cancer cells, and their subsequent invasion of otherwise healthy organs.
When the researchers carried out in vitro experiments in cells, they found that applying miR-96 and miR-182 decreased the expression of Palladin levels, in turn reducing the ability of breast cancer cells to migrate and invade other tissue.

They then developed a method to deliver engineered microRNAs to breast cancer tumours. They embedded nanoparticles containing the microRNAs into a hydrogel scaffold, which they then implanted into mice.
They found that this allowed efficient and precise delivery of the microRNAs to a target breast cancer tumour site. The treatment resulted in a dramatic reduction in breast cancer metastasis, said Artzi.
"We can locally change the cells in order to prevent metastasis from occurring," she said.