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Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer

Therapy-induced neuroendocrine prostate cancer (NEPC) is a highly lethal variant of prostate cancer that is increasing in incidence with the increased use of next-generation of androgen receptor (AR) pathway inhibitors. It arises via a reversible trans-differentiation process, referred to as neuroen...

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Autores principales: Sreekumar, Amritha, Saini, Sharanjot
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879360/
https://www.ncbi.nlm.nih.gov/pubmed/36711033
http://dx.doi.org/10.3389/fcell.2023.1075707
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author Sreekumar, Amritha
Saini, Sharanjot
author_facet Sreekumar, Amritha
Saini, Sharanjot
author_sort Sreekumar, Amritha
collection PubMed
description Therapy-induced neuroendocrine prostate cancer (NEPC) is a highly lethal variant of prostate cancer that is increasing in incidence with the increased use of next-generation of androgen receptor (AR) pathway inhibitors. It arises via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED), wherein prostate cancer cells show decreased expression of AR and increased expression of neuroendocrine (NE) lineage markers including enolase 2 (ENO2), chromogranin A (CHGA) and synaptophysin (SYP). NEPC is associated with poor survival rates as these tumors are aggressive and often metastasize to soft tissues such as liver, lung and central nervous system despite low serum PSA levels relative to disease burden. It has been recognized that therapy-induced NED involves a series of genetic and epigenetic alterations that act in a highly concerted manner in orchestrating lineage switching. In the recent years, we have seen a spurt in research in this area that has implicated a host of transcription factors and epigenetic modifiers that play a role in driving this lineage switching. In this article, we review the role of important transcription factors and chromatin modifiers that are instrumental in lineage reprogramming of prostate adenocarcinomas to NEPC under the selective pressure of various AR-targeted therapies. With an increased understanding of the temporal and spatial interplay of transcription factors and chromatin modifiers and their associated gene expression programs in NEPC, better therapeutic strategies are being tested for targeting NEPC effectively.
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spelling pubmed-98793602023-01-27 Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer Sreekumar, Amritha Saini, Sharanjot Front Cell Dev Biol Cell and Developmental Biology Therapy-induced neuroendocrine prostate cancer (NEPC) is a highly lethal variant of prostate cancer that is increasing in incidence with the increased use of next-generation of androgen receptor (AR) pathway inhibitors. It arises via a reversible trans-differentiation process, referred to as neuroendocrine differentiation (NED), wherein prostate cancer cells show decreased expression of AR and increased expression of neuroendocrine (NE) lineage markers including enolase 2 (ENO2), chromogranin A (CHGA) and synaptophysin (SYP). NEPC is associated with poor survival rates as these tumors are aggressive and often metastasize to soft tissues such as liver, lung and central nervous system despite low serum PSA levels relative to disease burden. It has been recognized that therapy-induced NED involves a series of genetic and epigenetic alterations that act in a highly concerted manner in orchestrating lineage switching. In the recent years, we have seen a spurt in research in this area that has implicated a host of transcription factors and epigenetic modifiers that play a role in driving this lineage switching. In this article, we review the role of important transcription factors and chromatin modifiers that are instrumental in lineage reprogramming of prostate adenocarcinomas to NEPC under the selective pressure of various AR-targeted therapies. With an increased understanding of the temporal and spatial interplay of transcription factors and chromatin modifiers and their associated gene expression programs in NEPC, better therapeutic strategies are being tested for targeting NEPC effectively. Frontiers Media S.A. 2023-01-12 /pmc/articles/PMC9879360/ /pubmed/36711033 http://dx.doi.org/10.3389/fcell.2023.1075707 Text en Copyright © 2023 Sreekumar and Saini. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sreekumar, Amritha
Saini, Sharanjot
Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
title Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
title_full Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
title_fullStr Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
title_full_unstemmed Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
title_short Role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
title_sort role of transcription factors and chromatin modifiers in driving lineage reprogramming in treatment-induced neuroendocrine prostate cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879360/
https://www.ncbi.nlm.nih.gov/pubmed/36711033
http://dx.doi.org/10.3389/fcell.2023.1075707
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