Critical Steps in Epithelial-Mesenchymal Transition as Target for Cancer Treatment

Epithelial-mesenchymal transition (EMT) is one of key triggers of metastasis in different malignant tumors and thereby represents a promising target to abrogate cancer progression. Herein, we aimed to systematize the information regarding steps of EMT that can be druggable and potential therapeutics that can be used to suppress epithelial-mesenchymal plasticity. EMT can be targeted through its suppression or reversal in cancer cells directly. Despite a number of studies that demonstrate a high efficiency of EMT suppression or reversal (mesenchymal-epithelial transition, MET) and inhibition of cancer progression using natural and chemically-synthesized compounds, these strategies are challenging due to potential unfavorable effects on normal tissues because of EMT involvement in physiological processes and promoting metastasis in which MET is needed for switching from micrometastasis to macrometastasis. The most promising and “safe” strategies to overcome EMT-related cancer progression can be targeting oncogenic mutations that lead to the induction of EMT, reprogramming tumor microenvironment towards anti-tumor state or suppression of inflammation, and differentiation of cancer cells to a completely mesenchymal phenotype or other cell types. However, further preclinical and clinical studies are needed to ascertain whether these approaches are safe and effective.