Novel gene therapy may check spread of breast cancer

Researchers are in the process of developing a new gene therapy technique that could be used alongside chemotherapy to treat early-stage breast cancer tumours before they spread.

The new technique uses microRNAs -- small noncoding RNA molecules that regulate gene expression -- to control metastasis or the spread of the disease, which is the leading cause of mortality in women with breast cancer.

"If 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," said research scientist Natalie Artzi at Massachusetts Institute of Technology (MIT) in the US. 

To identify the specific microRNAs that play a role in breast cancer progression and that could therefore potentially be used to suppress metastasis, the team first carried out an extensive bioinformatics analysis.

The analysis revealed a genetic variant single nucleotide polymorphisms (SNPs), known as rs1071738, which influences metastasis. This SNP was found to disrupt the binding of two microRNAs, miR-96 and miR-182. 

This disruption in turn prevented the two microRNAs from controlling the expression of a protein called Palladin, which has been known to play a key role in the migration of breast cancer cells, and their subsequent invasion of otherwise healthy organs, the researchers noted.

In vitro experiments in cells showed 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.

"Previous research had discussed the role of Palladin in controlling migration and invasion (of cancer cells). But the new study could pinpoint the critical role of these microRNAs in stopping the spread of breast cancer," Artzi said.

Further, the researchers developed a method to deliver the engineered microRNAs to breast cancer tumours. They embedded nanoparticles containing the microRNAs into a hydrogel scaffold, which they then implanted into mice.

The method 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, Artzi stated.

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.

"The research offers the potential for combined experimental therapeutics with traditional chemotherapy in cancer metastasis," Julie Teruya-Feldstein, Professor at Mount Sinai Hospital in New York, said in a comment. 

The findings were described in the paper published in the journal Nature Communications.