Fig. 2: Strategies to target EMP in cancer.

Various strategies for targeting cancer cell epithelial–mesenchymal plasticity (EMP) exist across the spectrum of cancer pathogenesis and progression. These include various types of action: aiming towards a differentiated phenotype (yellow) either by blocking (initial) epithelial–mesenchymal transition (EMT), thus avoiding invasive escape, intravasation, and extravasation (1), or by driving EMT-positive dormant cells through mesenchymal–epithelial transition (MET) to make them responsive to standard-of-care therapies and/or immunotherapies (2), or aiming towards an undifferentiated mesenchymal phenotype (red) by blocking MET, which is required for metastatic outgrowth at the target site (3), or by driving cells towards extreme EMT to maintain them in a dormant state (4), with the opportunity to directly target the hybrid epithelial/mesenchymal (E/M) or mesenchymal (M) phenotypes based on the identified unique vulnerabilities, for example, in their metabolism (5). Additional strategies include blocking plasticity entirely to freeze cells in the current state (plastistatic therapy) (6) and inducing the transdifferentiation of cancer cells into non-proliferating cells such as adipocytes (7; depicted in green).