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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 devel...

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Detalles Bibliográficos
Autores principales: Voon, Dominic C., Huang, Ruby Y., Jackson, Rebecca A., Thiery, Jean P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496500/
https://www.ncbi.nlm.nih.gov/pubmed/28544151
http://dx.doi.org/10.1002/1878-0261.12082
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author Voon, Dominic C.
Huang, Ruby Y.
Jackson, Rebecca A.
Thiery, Jean P.
author_facet Voon, Dominic C.
Huang, Ruby Y.
Jackson, Rebecca A.
Thiery, Jean P.
author_sort Voon, Dominic C.
collection PubMed
description 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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spelling pubmed-54965002017-07-18 The EMT spectrum and therapeutic opportunities Voon, Dominic C. Huang, Ruby Y. Jackson, Rebecca A. Thiery, Jean P. Mol Oncol Reviews 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. John Wiley and Sons Inc. 2017-06-19 2017-07 /pmc/articles/PMC5496500/ /pubmed/28544151 http://dx.doi.org/10.1002/1878-0261.12082 Text en © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Voon, Dominic C.
Huang, Ruby Y.
Jackson, Rebecca A.
Thiery, Jean P.
The EMT spectrum and therapeutic opportunities
title The EMT spectrum and therapeutic opportunities
title_full The EMT spectrum and therapeutic opportunities
title_fullStr The EMT spectrum and therapeutic opportunities
title_full_unstemmed The EMT spectrum and therapeutic opportunities
title_short The EMT spectrum and therapeutic opportunities
title_sort emt spectrum and therapeutic opportunities
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496500/
https://www.ncbi.nlm.nih.gov/pubmed/28544151
http://dx.doi.org/10.1002/1878-0261.12082
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