Gene therapy technique may help prevent cancer metastasis

The uncontrollable spread of malignant cells around the body, known as metastasis, is the leading cause of mortality in individuals with cancer.

However, in a release by Massachusetts Institute of Technology (MIT), a new gene therapy is being developed by that university's researchers along with researchers from Tel-Aviv University in Israel. This therapy, the researchers say, prevents breast cancer tumours from metastasising.

The treatment, described in a paper published in the journal Nature Communications, uses microRNAs — small non-coding RNA molecules that regulate gene expression — to control metastasis.

The therapy could be used alongside chemotherapy to treat early-stage breast cancer tumours before they spread. “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,” Natalie Artzi, the first author of the paper told MIT's newsroom.

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 data sets: one for known SNPs (pronounced snip); 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 revealed 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.

The researchers 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, says Artzi.

To increase the effectiveness of the treatment even further, the researchers then added the chemotherapy drug cisplatin to the nanoparticles. This led to a significant reduction in both the growth of the primary tumour, and its metastasis.