Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance

Despite advancements in understanding cancer pathogenesis and the development of many effective therapeutic agents, resistance to drug treatment remains a widespread challenge that substantially limits curative outcomes. The historical focus on genetic evolution under drug “pressure” as a key driver...

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Main Authors: Chames Kermi, Lena Lau, Azar Asadi Shahmirzadi, Marie Classon
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.826461/full
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author Chames Kermi
Lena Lau
Azar Asadi Shahmirzadi
Marie Classon
author_facet Chames Kermi
Lena Lau
Azar Asadi Shahmirzadi
Marie Classon
author_sort Chames Kermi
collection DOAJ
description Despite advancements in understanding cancer pathogenesis and the development of many effective therapeutic agents, resistance to drug treatment remains a widespread challenge that substantially limits curative outcomes. The historical focus on genetic evolution under drug “pressure” as a key driver of resistance has uncovered numerous mechanisms of therapeutic value, especially with respect to acquired resistance. However, recent discoveries have also revealed a potential role for an ancient evolutionary balance between endogenous “viral” elements in the human genome and diverse factors involved in their restriction in tumor evolution and drug resistance. It has long been appreciated that the stability of genomic repeats such as telomeres and centromeres affect tumor fitness, but recent findings suggest that de-regulation of other repetitive genome elements, including retrotransposons, might also be exploited as cancer therapy. This review aims to present an overview of these recent findings.
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spelling doaj.art-8371b0dfbd894045b742fef485f3f5bc2022-12-22T01:54:00ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-05-011010.3389/fcell.2022.826461826461Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug ResistanceChames KermiLena LauAzar Asadi ShahmirzadiMarie ClassonDespite advancements in understanding cancer pathogenesis and the development of many effective therapeutic agents, resistance to drug treatment remains a widespread challenge that substantially limits curative outcomes. The historical focus on genetic evolution under drug “pressure” as a key driver of resistance has uncovered numerous mechanisms of therapeutic value, especially with respect to acquired resistance. However, recent discoveries have also revealed a potential role for an ancient evolutionary balance between endogenous “viral” elements in the human genome and diverse factors involved in their restriction in tumor evolution and drug resistance. It has long been appreciated that the stability of genomic repeats such as telomeres and centromeres affect tumor fitness, but recent findings suggest that de-regulation of other repetitive genome elements, including retrotransposons, might also be exploited as cancer therapy. This review aims to present an overview of these recent findings.https://www.frontiersin.org/articles/10.3389/fcell.2022.826461/fulltransposable elementsdrug resistanceepigenetic regulationrestriction factorsR-loopsnucleic acid sensing
spellingShingle Chames Kermi
Lena Lau
Azar Asadi Shahmirzadi
Marie Classon
Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
Frontiers in Cell and Developmental Biology
transposable elements
drug resistance
epigenetic regulation
restriction factors
R-loops
nucleic acid sensing
title Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
title_full Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
title_fullStr Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
title_full_unstemmed Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
title_short Disrupting Mechanisms that Regulate Genomic Repeat Elements to Combat Cancer and Drug Resistance
title_sort disrupting mechanisms that regulate genomic repeat elements to combat cancer and drug resistance
topic transposable elements
drug resistance
epigenetic regulation
restriction factors
R-loops
nucleic acid sensing
url https://www.frontiersin.org/articles/10.3389/fcell.2022.826461/full
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