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Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance

Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a...

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Autores principales: Altschuler, Joshua, Stockert, Jennifer A., Kyprianou, Natasha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924036/
https://www.ncbi.nlm.nih.gov/pubmed/33672595
http://dx.doi.org/10.3390/ijms22042100
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author Altschuler, Joshua
Stockert, Jennifer A.
Kyprianou, Natasha
author_facet Altschuler, Joshua
Stockert, Jennifer A.
Kyprianou, Natasha
author_sort Altschuler, Joshua
collection PubMed
description Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands. As such, AR remains the main driver of therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). While androgen deprivation therapy (ADT), in combination with microtubule-targeting taxane chemotherapy, offers survival benefits in patients with mCRPC, therapeutic resistance invariably develops, leading to lethal disease. Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes and also to the development of biomarker signatures of predictive value. The interconversions between epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) navigate the prostate tumor therapeutic response, and provide a novel targeting platform in overcoming therapeutic resistance. Both microRNA (miRNA)- and long non-coding RNA (lncRNA)-mediated mechanisms have been associated with epigenetic changes in prostate cancer. This review discusses the current evidence-based knowledge of the role of the phenotypic transitions and novel molecular determinants (non-coding RNAs) as contributors to the emergence of therapeutic resistance and metastasis and their integrated predictive value in prostate cancer progression to advanced disease.
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spelling pubmed-79240362021-03-03 Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance Altschuler, Joshua Stockert, Jennifer A. Kyprianou, Natasha Int J Mol Sci Review Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands. As such, AR remains the main driver of therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). While androgen deprivation therapy (ADT), in combination with microtubule-targeting taxane chemotherapy, offers survival benefits in patients with mCRPC, therapeutic resistance invariably develops, leading to lethal disease. Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes and also to the development of biomarker signatures of predictive value. The interconversions between epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) navigate the prostate tumor therapeutic response, and provide a novel targeting platform in overcoming therapeutic resistance. Both microRNA (miRNA)- and long non-coding RNA (lncRNA)-mediated mechanisms have been associated with epigenetic changes in prostate cancer. This review discusses the current evidence-based knowledge of the role of the phenotypic transitions and novel molecular determinants (non-coding RNAs) as contributors to the emergence of therapeutic resistance and metastasis and their integrated predictive value in prostate cancer progression to advanced disease. MDPI 2021-02-20 /pmc/articles/PMC7924036/ /pubmed/33672595 http://dx.doi.org/10.3390/ijms22042100 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Altschuler, Joshua
Stockert, Jennifer A.
Kyprianou, Natasha
Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance
title Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance
title_full Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance
title_fullStr Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance
title_full_unstemmed Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance
title_short Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance
title_sort non-coding rnas set a new phenotypic frontier in prostate cancer metastasis and resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924036/
https://www.ncbi.nlm.nih.gov/pubmed/33672595
http://dx.doi.org/10.3390/ijms22042100
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AT kyprianounatasha noncodingrnassetanewphenotypicfrontierinprostatecancermetastasisandresistance