Targeting the Twist and Wnt signaling pathways in metastatic breast cancer

Breast cancer is the leading cause of cancer-related deaths in the United States with over 232,000 new diagnoses expected in 2014 and almost 40,000 deaths. While treatment of primary breast cancer is often well-managed with surgery and radiation, metastatic breast cancer (MBC) that has spread to the brain, bones, liver, and lungs is often incurable. One of the major challenges in the treatment of breast cancer is the presence of a subpopulation of cancer cells that are chemoresistant and metastatic. Given that metastasis is the driving force behind mortality for breast cancer patients, it is essential to identify the characteristics of these aberrant cancer cells that allow them to spread to distant sites in the body and develop into metastatic tumors. Understanding the metastatic mechanisms driving cancer cell dispersal will open the door to developing novel therapies that prevent metastasis and improve long-term outcomes for patients. In this review we assess the feasibility of targeting the Twist and Wnt signaling pathways in breast cancer. These pathways mediate epithelial-mesenchymal transition (EMT), a process that can give rise to chemoresistance. We review potential treatment strategies for targeting EMT and drug resistance as well as the problems that may arise with these targeted delivery therapeutic approaches. Finally, we examine recent advances in the field, including nanoparticle delivery and small interfering RNA (siRNA) technology, and discuss the impact that these approaches may have on translating much needed therapeutic approaches into the clinic, for the benefit of patients battling MBC. (C) 2014 Elsevier Ireland Ltd. All rights reserved.