Novel targeted therapies for triple negative breast cancers based on the use of engineered nanoparticles
Triple negative breast cancers belong to the basal-like subtype and account for ~15% of breast cancers. Basal-like breast cancers mostly affect Australian women under 50 years old and have the poorest survival rate of all breast cancers. The ability of basal-like breast cancers to disseminate throughout the body and their high resistance to chemotherapy makes them difficult to treat. Thus, there is an urgent need to develop novel treatments that could reduce disease burden and mortality. Here we propose the development of a novel and revolutionary therapy based on the use of nanoparticles containing chemotherapeutic agents used in the clinic for breast cancer in combination with synthetic inhibitory peptides (interference peptides, iPeps). These iPeps are able to specifically bind, and inhibit proteins that are present in high amounts in basal-like breast cancer cells but not in normal cells and that are known to produce chemotherapy resistance. One of these proteins is EN1 and we will bind EN1-iPeps on the surface of the nanoparticles. The engineered construct will efficiently kill basal-like breast cancer cells, especially those most resistant to chemotherapy. The project will be carried out firstly in breast cancer cells, and then the successful combinations will be tested in animals. It is hoped that from this project, new successful treatments for basal-like breast cancers will emerge that can be easily applied in patients.