Abstract P2-07-04: Treatment of metastatic breast cancer using two nanoparticles combined with siRNA targeting Twist1 to inhibit EMT

Breast cancer is the 2nd leading cause of cancer related deaths among women in the US with over 240,000 diagnoses and 40,000 deaths expected in 2014. Among the more serious and deadly forms of breast cancer are the Triple Negative Breast Cancers (TNBC) (ER-, PR-, HER2-). Mortality rates among patients rise dramatically when these cancers spread beyond the primary tumor site. Therefore reduction of tumor cell dispersion is a key component to minimizing mortality rates. Epithelial-Mesenchymal Transition (EMT) is the process by which cancer cells downregulate proteins associated with cell to cell adhesion (e.g. E-cadherin) resulting in cells that are able to detach from neighboring cancer cells, invade adjacent tissue, and eventually enter the circulatory system or lymphatics. The process of EMT is tightly regulated by the transcription factor Twist1, which is often overexpressed in breast cancer. Therefore, Twist1 serves as an excellent therapeutic target whose downregulation would result in fewer metastatic cancer cells and correspondingly reduce cancer mortality. Our lab has designed and tested (in vitro) two siRNA based therapeutics that target Twist1 in a TNBC cell line (SUM 1315). These siRNA molecules have been strategically designed and modified to make them resistant to degradation, enhance silencing effects and diminish their immunogenicity. To overcome the inherent problems with delivery of siRNA (both in vitro and in vivo) we have been testing two nanoparticle delive...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Poster Session Abstracts Source Type: research