Epithelial-mesenchymal transition (EMT) is a highly dynamic, multistep process implicated in various physio-pathological conditions, including chronic inflammation, fibrogenic diseases, and cancer. In tumors, the acquisition of EMT provides increased migratory-invasive abilities. Moreover, more recently, EMT was shown to mediate the acquisition of chemoresistance linked to cancer stem cell-like features. EMT induction and reversal are triggered by different stimuli, including diffusible mediators such as TGFß1 as well as changes in the biochemical and biomechanical composition of the extracellular matrix (ECM). Moreover, the role of exosomes as the main effectors of cell-to-cell communication has been recently elucidated. EMT induction depends on the regulation of EMT master genes (i.e., Snail), whose expression and activity are under the control of epigenetic mechanisms.
Due to the central role of EMT in the pathogenesis of fibrotic diseases and cancer, growing evidence suggests that the pharmacological inhibition of main mechanisms controlling ECM may be a valid therapeutic approach. However, attempts to target EMT per se or in combination with other treatments, have failed in most cases. One possible explanation may reside in incomplete knowledge of the underlying mechanisms or the lack of appropriate systems for the delivery of therapies targeting EMT. Indeed, the standard therapeutic strategies may present a variety of drawbacks, such as low specificity, drug resistance, rapid drug clearance, and biodegradation, which can lead to treatment failure.
In the last years, the use of drug delivery systems based on nanomaterials has improved the properties of a variety of bioactive therapies, including drugs, peptides, and antibodies. Mainly, advances in material sciences led to the development of different nanomaterials that can be employed to improve the biodistribution of drugs and their accumulation at the target site. Encouraging results were obtained in both preclinical and clinical studies.
This proposed Research Topic will be based on our previous Research Topic entitled
‘Molecular Mechanisms and New Therapeutic Targets in Epithelial to Mesenchymal Transition (EMT) and Fibrosis’. In this new special number, we will analyze novel molecular mechanisms that regulate EMT in fibrosis, inflammatory pathologies, and cancer with a special focus on the discovery and characterization of innovative "epidrugs" and nanomedicines based on EMT inhibition. We encourage basic and translational scientists working in related research fields to submit original studies or review articles.