Triple-negative breast cancer: understanding Wnt signaling in drug resistance

Triple-negative breast cancer (TNBC) is not as prevalent as hormone receptor or HER2-positive breast cancers and all receptor tests come back negative. More importantly, the heterogeneity and complexity of the TNBC on the molecular and clinical levels have limited the successful development of novel therapeutic strategies and led to intrinsic or developed resistance to chemotherapies and new therapeutic agents. Studies have demonstrated deregulation of Wnt/β-catenin signaling in tumorigenesis which plays decisive roles at the low survival rate of patients and facilitates resistance to currently existing therapies. This review summarizes mechanisms of Wnt/β-catenin signaling for resistance development in TNBC, the complex interaction between Wnt/β-catenin signaling, and the transactivated receptor tyrosine kinase (RTK) signaling pathways, lymphocytic infiltration, epithelial-mesenchymal transition (EMT), and induction of metastasis. Such associations and how these pathways interact in the development and progression of cancer have led to the careful analysis and development of new and effective combination therapies without generating significant toxicity and resistance.