Highlights
- The nanodelivery system targets HER2-positive breast cancer and reduces production of protein MED1.
- Stopping production of the protein MED1 reduces tumor growth.
- The treatment can sensitize the cancer cells to treatment with tamoxifen, a known therapy for estrogen-driven cancer. Multifunctional RNA nanoparticles that could overcome treatment resistance in breast cancer, can make existing treatments more effective in these patients. Researchers at the University of Cincinnati (UC) College of Medicine led by Xiaoting Zhang, PhD, associate professor in the Department of Cancer Biology at the UC College of Medicine, shows that using a nanodelivery system to target HER2-positive breast cancer and stop production of the protein MED1 could slow tumor growth, stop cancer from spreading and sensitize the cancer cells to treatment with tamoxifen.
- Xiaoting Zhang et al., Study shows nanoparticles could be used to overcome treatment-resistant breast cancer, ACS Nano (2016).
MED1 co-produces (co-expresses) and co-amplifies with HER2 in most cases, and Zhang's previous studies have shown their interaction plays key roles in anti-estrogen treatment resistance.
"Most breast cancers express estrogen receptors, and the anti-estrogen drug tamoxifen has been widely used for their treatment," says Zhang, who is also a member of the Cincinnati Cancer Center and the UC Cancer Institute.
"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."
Zhang and researchers in his lab found that these RNA nanoparticles were able to selectively bind to HER2-overexpressing breast tumors, eliminating MED1 expression and significantly decreasing estrogen receptor-controlled target gene production. The RNA nanoparticles not only reduced the growth and spread of the HER2-overexpressing breast cancer tumors, but also sensitized them to tamoxifen treatment.
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.
Reference
Source-Medindia