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Targeting epithelial-mesenchymal transition: therapeutic reversal of the cancer stem cell phenotype

John P Fruehauf and Ming C Liau

Malignant tumors are composed of various cell types, including heterogeneous mixtures of neoplastic cells. Epithelial tissues that undergo transformation exist in an adverse environment where oxygen and nutrient supply is low, resulting in the upregulation of survival pathways, many of which are driven by hypoxia inducible factors-1 and -2. The intersection between downstream survival pathways driven by hypoxia inducible factors, stem cell characteristics of cancer and epithelial–mesenchymal transition has recently come to light. Insights into these processes are beginning to yield exciting new avenues for targeted therapies that promise to overcome treatment resistance.