Grant: Project Grant

Breast cancer remains a leading cause of death in women in the world. The triple negative breast cancer (TNBC) accounts for only 15-20% of all breast cancers but disproportionately accounts for the majority of breast cancer related deaths. TNBC patients are prone to recurrence between the first and third years post treatment with majority of deaths within the first five years post therapy. Chemotherapy is currently the mainstay of systemic medical treatment for TNBC, which associates with rapid drug-resistance, enrichment of cancer stem cells (CSCs), and disease recurrence. Two CSC subtypes have recently been shown to coexist and both exhibit strong tumor regeneration capacity. Using multiple methods, we have recently observed that two specific signaling pathways must be co-inhibited in the presence of a chemotherapeutic drug to kill bulk cancer cells and suppress both CSC subtypes. Concurrently, the dual inhibition also promotes anti-cancer immunity. The goal of this proposed work is to study the cooperative roles of this new combination therapy, to develop novel, clinically translatable nano-therapeutics, and to evaluate their efficacy in clinically relevant animal models. It is expected that completion of this proposed work will lead to a new and tangible approach to effectively treat TNBC to reduce disease relapse.