Researchers from the University of Cincinnati College of Medicine have developed RNA nanoparticles that show promise in overcoming treatment-resistant breast cancer. The team’s work was published in ACS Nano.
The researchers used a nanocarrier to target HER2-positive breast cancer and stop the production of a specific protein to prevent metastasis and render the cancer cells vulnerable to tamoxifen, a therapy for estrogen-driven cancer.
“Most breast cancers express estrogen receptors, and the anti-estrogen drug tamoxifen has been widely used for their treatment,” lead researcher Xiaoting Zhang said in prepared remarks. “Unfortunately, up to half of all estrogen receptor-positive tumors are either unresponsive or later develop resistance to the therapy. In this study, we have developed a highly innovative design that takes advantage of the co-overexpression of HER2 and MED1 in these tumors.”
The RNA nanoparticles selectively bound to breast tumors that overly expressed HER2. Upon binding to the tumors, the nanoparticles suppressed estrogen receptor-controlled target gene production and eliminated MED1 expression.
“These bio-safe nanoparticles efficiently targeted and penetrated into HER2-overexpressing tumors after administration in animal models,” Zhang said. “In addition, these nanoparticles also led to a dramatic reduction in the cancer stem cell content of breast tumors when combined with tamoxifen treatment. Cancer stem cells, as you know, are tumor-causing cells that are known to play essential roles in tumor spread, recurrence and therapy resistance. Eliminating these cells could represent an improved and more desirable treatment strategy for breast cancer patients.
“These findings are highly promising for potential clinical treatment of advanced metastatic and tamoxifen-resistant human breast cancer. Further studies are still needed and hopefully soon we’ll be able to test our nanoparticles in clinical trials at the UC Cancer Institute’s Comprehensive Breast Cancer Center.”