Figure 4.

Possible therapeutic strategies targeting EMT plasticity via epigenetic modification. In different stages of metastasis, EMT and MET play contradictory roles, highlighting the need for context-specific therapeutic modalities for distinct disease status. As the interactions between EMT-TFs and epigenetic regulators have been widely revealed, targeting epigenetic mechanisms to manipulate EMT will have a promising therapeutic potential. Possible strategies include manipulation of miR-200s or miR-34 or chromatin modifiers that modulate EMT-TFs. Recently, treatments targeting CTCs are also emerging as exemplified by ouabain and digitoxin, which are FDA-approved Na⁺/K⁺-ATPase inhibitors and are identified to dissociate CTC clusters that harbor distinct DNA methylation pattern. Besides, various conceptual strategies targeting EMT plasticity are also proposed, with some of them are already proved effective in preclinical settings.