MIT researchers are developing a combination therapy where gene therapy is delivered alongside chemotherapy to suppress breast cancer metastasis, the leading cause of death in women with breast cancer.
Previous research shows that microRNAs, small noncoding RNA molecules that regulate gene expression, can play a role in blocking the spread of cancer cells. The MIT team sought to identify specific mRNAs involved in breast cancer progression with the hope of harnessing them to tamp down on metastasis, according to a statement.
From a bioinformatics analysis, they found a genetic variant that disrupts the binding of two mRNAs, miR-96 and miR-182. This stops them from controlling the expression of the protein Palladin, which is known to drive the migration of breast cancer cells, according to the statement.
They applied the two mRNAs to lab cells and found that the application lowered Palladin levels and cut the ability of breast cancer cells to migrate and invade other cells, the researchers said in the statement.
"Previous research had discussed the role of Palladin in controlling migration and invasion (of cancer cells) but no one had tried to use microRNAs to silence those specific targets and prevent metastasis," said Natalie Artzi, a principal research scientist at MIT's Institute for Medical Engineering and Science and an assistant professor of medicine at Brigham and Women's Hospital, in the statement. "In this way we were able to pinpoint the critical role of these microRNAs in stopping the spread of breast cancer."
They then developed a method to boost the therapy’s efficacy and to deliver it directly to breast tumors: They embedded nanoparticles containing the mRNAs and the chemotherapy drug cisplatin into a hydrogel scaffold, which they implanted into mice. This caused the primary tumor to shrink in addition to “significantly” reducing metastasis.
While Artzi said the next steps include moving onto larger models and eventually to clinical trials, “there is still a long way to go.”