Approaches to induce tumor differentiation often result in manageable and therapy‐naïve cellular states in cancer cells. This transformation is achieved by activating pathways that drive tumor cells away from plasticity, a state that commonly correlates with enhanced aggression, metastasis and resistance to therapy. Here, we discuss signaling pathways, epigenetics and non‐coding RNAs as three main regulatory levels with the potential to drive tumor differentiation and hence as potential targets in differentiation therapy approaches. The success of an effective therapeutic regimen in (...) one cancer, however, does not necessarily sustain across cancer types; a phenomenon largely resulting from heterogeneity in the genetic and physiological landscapes of tumor types necessitating an approach designed for each cancer's unique genetic and phenotypic build‐up. (shrink)

Cells can transit between a range of stable epithelial and mesenchymal states and this has allowed the evolution of complex body forms. Epithelial to mesenchymal transition (EMT) and its reverse, mesenchymal to epithelial transition (MET), occur sequentially in development and organogenesis. EMT often accompanies transitions between stem‐like cells and their more differentiated progeny, as occurs at gastrulation, although the relevance of this had not been clarified. New findings from the cancer and cell reprogramming fields suggest that EMT and MET can (...) act as essential portals to stem cell character. Here, we review these findings in the broader context of EMT and MET with emphasis on stem cell biology. Using the heart as an example, we also explore the potential role of EMT/MET in organ regeneration. Understanding EMT and MET at a network level will give us new tools to probe stem cell character and enhance tissue repair. (shrink)