The EMT spectrum and therapeutic opportunities

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.

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