Targeting Epithelial-to-Mesenchymal Transition for Breast Cancer Stem Cells Therapeutics

Abstract

Metastasis of breast cancer cells involves the dissemination from primary tumor sites and migration to distant organs forming secondary tumors, which causes a major hurdle to breast cancer treatment. Epithelial-to-Mesenchymal Transition (EMT) has been extensively studied in mammalian embryogenesis and disease conditions such as breast cancer invasion and metastasis. Any disturbance in the fine balance between the epithelial and mesenchymal phenotypes of breast cancer cells promotes metastatic development. EMT-induction in aggressive breast cancer cells gives rise to a subset of breast cancer stem cells (CSCs) which are highly migratory in nature and leads to resistance against chemotherapy. In this chapter, we analyze the EMT pathways and the interactions of EMT genes involved in breast cancer progression. We also analyze the promoter interactions of EMT genes with EMT transcription factors using in silico analysis and validate the mRNA expression of EMT genes in various breast cancer cells in literature. Finally, we analyze the interactions between EMT-TFs and genes with novel small molecules at preclinical stages and clinically approved drugs that can effectively target the breast CSCs to treat aggressive breast cancers. This study was intended to explore molecular EMT factors on breast CSCs that can be effectively targeted to mitigate breast cancer by repurposing of drugs.