Scientists in the University of Cincinnati (UC) College of Medicine state they have been able to generate multifunctional RNA nanoparticles that could conquer treatment resistance in breast cancer, potentially making existing remedies more effective in these patients.
Their study (“Overcoming Tamoxifen Resistance of Human Breast Cancer by Targeted Gene Silencing using Multifunctional pRNA Nanoparticles”) is published on the internet in the American Chemical Society’s ACS Nano. It had been led by Xiaoting Zhang, PhD, associate professor within the Department of Cancer Biology at the UC College associated with Medicine, and shows that using a nanodelivery system to target HER2-positive breast cancer and stop production of the protein MED1 could sluggish tumor growth, stop cancer from spreading and sensitize the cancer cells to treatment with tamoxifen, the known therapy for estrogen-driven cancer.
MED1 is a protein often produced at abnormally high amounts in breast cancer cells that when eliminated is found to stop malignancy cell growth. HER2-positive breast cancer involves amplification of a gene encoding, or programming, the protein known as human skin growth factor receptor 2, which also promotes the particular growth of cancer cells. MED1 co-produces (co-expresses) plus co-amplifies with HER2 in most cases, and Zhang’s previous correctly shown their interaction plays key roles in anti-estrogen treatment resistance.
“Most breast cancers convey estrogen receptors, and the anti-estrogen drug tamoxifen has been popular for their treatment, ” says Dr . zhang, who is the member of the Cincinnati Cancer Center and the UC Malignancy Institute. “Unfortunately, up to half of all estrogen receptor-positive cancers are either unresponsive or later develop resistance to the treatment. In this study, we have developed a highly innovative design that will takes advantage of the co-overexpression of HER2 and MED1 during these tumors. ”
Dr . Zhang and scientists in his lab found that these RNA nanoparticles were able to selectively bind to HER2-overexpressing breast tumors, eliminating MED1 appearance and significantly decreasing estrogen receptor-controlled target gene creation. The RNA nanoparticles not only reduced the growth plus spread of the HER2-overexpressing breast cancer tumors, but also sensitized these to tamoxifen treatment.
“These bio-safe nanoparticles effectively targeted and penetrated into HER2-overexpressing tumors after management in animal models, ” he says. “In addition, these types of nanoparticles also led to a dramatic reduction in the malignancy stem cell content of breast tumors when coupled with tamoxifen treatment. Cancer stem cells, as you know, are tumor-causing cells that are known to play essential roles in growth spread, recurrence and therapy resistance. Eliminating these cellular material could represent an improved and more desirable treatment strategy for cancer of the breast patients.
“These findings are highly guaranteeing for potential clinical treatment of advanced metastatic and tamoxifen-resistant human breast cancer. Further studies are still needed and ideally soon we’ll be able to test our nanoparticles in scientific trials at the UC Cancer Institute’s Comprehensive Breast Cancer Middle. ”