siRNA-toting nanoparticles inhibit breast cancer metastasis

Researchers at Case Western Reserve University combined finely crafted nanoparticles with one of nature's potent disrupters to prevent the spread of triple-negative breast cancer in mouse models.

The highly aggressive cancer subtype is difficult to manage and, currently, the FDA has no approved targeted treatments. But striking results from a new study, published in the journal Cancer Research make the researchers optimistic they have a potential game-changer for triple negative cancer and more.

"There are multiple targets within a cell," said William Schiemann, professor of oncology at the Case Western Reserve School of Medicine and the Case Comprehensive Cancer Center, and a leader of the research. "With this technology, we can target any gene or any location, for other cancers, more diseases - potentially even immunology-based diseases."

Regular injections of nanoparticles carrying siRNA silenced the gene that regulates expression of the protein β3 integrin. Expression of β3 integrin in the cell-development process called the endothelial-mesenchymal transition (EMT), is essential for the cancer to spread from its primary tumor.

Nearly 15 percent of breast cancers in the United States are triple negative, and the subtype is most prevalent among African-American women in their 20s and 30s

According to the National Cancer Institute, the five-year survival rate for women whose cancer is discovered early and contained to a primary tumor is 98 percent. But, the survival rate for those diagnosed with distant metastases plummets to less than 25 percent.

Overall estimates of breast cancer in the U.S. Women

In 2015, it is estimated that among U.S. women there will be:

- 231,840 new cases of invasive breast cancer (This includes new cases of primary breast cancer among survivors, but not recurrence of original breast cancer among survivors.)
- 60,290 new cases of in situ breast cancer (This includes ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Of those, about 83 percent will be DCIS. DCIS is a non-invasive breast cancer and LCIS is a condition that increases the risk of invasive breast cancer. Learn more about DCIS and LCIS.)
- 40,290 breast cancer deaths

###
American Cancer Society. Cancer Facts and Figures 2015. Atlanta, GA: American Cancer Society, 2015.

To try to tackle metastasis, Schiemann teamed with Zheng-Rong Lu, the M. Frank and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve, Jenny Parvani, now a postdoctoral investigator, PhD student Maneesh Gujrati and undergraduate student Margaret Mack.

Lu's lab has been developing lipid-based nanoparticles to deliver medicines to specific targets in the body for a decade. Lipids include fats and oils, but these organic molecules are also building blocks in cell structures and functions.