EMT: Present and future in clinical oncology

Abstract

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.

Sodium butyrate inhibits migration and induces AMPK‐mTOR pathway‐dependent autophagy and ROS‐mediated apoptosis via the miR‐139‐5p/Bmi‐1 axis in human bladder cancer cells

“…The EMT is regarded as a vital regulator in cancer metastasis. Emerging evidence supports that the switch between epithelial and mesenchymal states is an indicator of the potential of metastasis and dissemination of tumor cells . E‐cadherin, N‐cadherin, Vimentin, and Snail are several markers of the EMT.…”

“…18 The epithelial-mesenchymal transition (EMT) is a vital process in cancer metastasis and is attracting increasing attention in basic research on cancer therapies. 19 Interestingly, Bmi-1 has been reported to be an important target of microRNAs that is closely relate to the reversal of EMT processes. 20 In addition, depletion of Bmi-1 pharmacologically and genetically induces cell death and triggers autophagy in other tumors.…”

Gemcitabine‐induced epithelial‐mesenchymal transition‐like changes sustain chemoresistance of pancreatic cancer cells of mesenchymal‐like phenotype

“…Taken together, these data show a correlation between the EMT status and gemcitabine resistance in mesenchymal PC cells. In this context, the development of specific novel drugs against EMT constitutes an important challenge . Several drugs being currently under development in clinical trials display an inhibitory effect on EMT.…”

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

“…Changes in cell adhesion, polarity, and cytoskeletal remodeling enhance tumor cell plasticity and migration, thus promoting tumor spread . EMT has been also associated with cancer drug resistance …”