Blocking Unexplored Breast Cancer Mutations Seen to Largely Stop Metastasis in Mice

Blocking Unexplored Breast Cancer Mutations Seen to Largely Stop Metastasis in Mice

Targeting often ignored mutations in breast cancer cells with gene therapy largely prevented the formation of metastasis — the one thing that transforms a breast tumor linked to good survival chances into a deadly disease.

When researchers treated mice with a combination of the genetic therapy and chemotherapy, the effects were even better.

These results, in the study, “Local microRNA delivery targets Palladin and prevents metastatic breast cancer,” were published in the journal Nature Communications.

Despite advances in breast cancer detection and treatment, researchers have not found a way to prevent breast tumors from metastasizing. Once a breast cancer starts spreading to other parts of the body, only about 20 percent of patients survive for longer than five years.

“The situation is bleak. Death rates from breast cancer remain high and relatively unchanged despite advances in medicine and technology,” Noam Shomron, the study’s senior author and a researcher at Tel Aviv University (TAU), said in a news release. “We wanted to find a way to stop metastasis from happening altogether.”

The team started by studying cancer mutations in databases, focusing on those other research efforts had omitted. Most often, studies focus on gene mutations present in the part of a gene coding for a protein.

Tel Aviv researchers, together with collaborators at Massachusetts Institute of Technology (MIT), focused instead on mutations in regions that scientists think control the activity of other genes. They found three mutations linked to metastasis.

Once the team knew identified these mutations,  it used mice with breast cancer to test a new approach, injecting microRNAs — small molecules that can silence or change the activity of a gene — to target the movement of tumor cells from primary to secondary sties.

Mice that were treated with two different microRNAs had considerably less, or no, evidence of metastasis. When microRNA treatment was combined with chemotherapy, the outcome was even better.

“We realized we had stopped breast cancer metastasis in a mouse model, and that these results might be applicable to humans,” said Shomron. “Our results are especially encouraging because they have been repeated several times at TAU and at MIT by independent groups.”