The EMT spectrum and therapeutic opportunities
Journal
Molecular Oncology
Journal Volume
11
Journal Issue
7
Pages
878-891
Date Issued
2017
Author(s)
Abstract
Carcinomas are phenotypically arrayed along an epithelial-mesenchymal transition (EMT) spectrum, a developmental program currently exploited to understand the acquisition of drug resistance through a re-routing of growth factor signaling. This review collates the current approaches employed in developing therapeutics against cancer-associated EMT, and provides an assessment of their respective strengths and drawbacks. We reflect on the close relationship between EMT and chemoresistance against current targeted therapeutics, with a special focus on the epigenetic mechanisms that link these processes. This prompts the hypothesis that carcinoma-associated EMT shares a common epigenetic pathway to cellular plasticity as somatic cell reprogramming during tissue repair and regeneration. Indeed, their striking resemblance suggests that EMT in carcinoma is a pathological adaptation of an intrinsic program of cellular plasticity that is crucial to tissue homeostasis. We thus propose a revised approach that targets the epigenetic mechanisms underlying pathogenic EMT to arrest cellular plasticity regardless of upstream cancer-driving mutations.
SDGs
Publisher
Wiley Blackwell
Type
review