EMT: Present and future in clinical oncology

Epithelial/mesenchymal transition (EMT) has emerged as a key regulator of metastasis by facilitating tumor cell invasion and dissemination to distant organs. Recent evidences support that the reverse mesenchymal/epithelial transition (MET) is required for metastatic outgrowth; moreover, the existence of hybrid epithelial/mesenchymal (E/M) phenotypes is increasingly being reported in different tumor contexts. The accumulated data strongly support that plasticity between epithelial and mesenchymal states underlies the dissemination and metastatic potential of carcinoma cells. However, the translation into the clinics of EMT and epithelial plasticity processes presents enormous challenges and still remains a controversial issue. In this review, we will evaluate current evidences for translational applicability of EMT and depict an overview of the most recent EMT in vivo models, EMT marker analyses in human samples as well as potential EMT therapeutic approaches and ongoing clinical trials. We foresee that standardized analyses of EMT markers in solid and liquid tumor biopsies in addition to innovative tools targeting the E/M states will become promising strategies for future translation to the clinical setting.Work in our laboratories is supported by grants from the Spanish Ministerio de Economía y Competitividad SAF2013-44739-R and SAF2016-76504-R (AC and FP), the Spanish Instituto de Salud Carlos III [RETIC-RD12/0036/0007, CIBERONC-CB16/12/00295 (AC); PI13/00132, PI16/00134 (GMB)] (all of them partly supported from EUFEDER funds), and Worldwide Cancer Research (WWCR, formerly AICR) WWCR 16-0295 (AC, PGS, and FP). PGS was funded by a postdoctoral contract from the Fundacion Científica AECC and presently from WWCR 16-0295.Peer reviewe