Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) has poor prognosis with limited treatment options, with little therapeutic progress made during the past several decades. DNA damage response (DDR) associated therapies, including radiation and inhibitors of DDR, demonstrate potential efficacy against TNBC, espec...

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Main Authors: Curtis A. Clark, Eddy S. Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.703802/full
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author Curtis A. Clark
Eddy S. Yang
Eddy S. Yang
Eddy S. Yang
author_facet Curtis A. Clark
Eddy S. Yang
Eddy S. Yang
Eddy S. Yang
author_sort Curtis A. Clark
collection DOAJ
description Triple-negative breast cancer (TNBC) has poor prognosis with limited treatment options, with little therapeutic progress made during the past several decades. DNA damage response (DDR) associated therapies, including radiation and inhibitors of DDR, demonstrate potential efficacy against TNBC, especially under the guidance of genomic subtype-directed treatment. The tumor immune microenvironment also contributes greatly to TNBC malignancy and response to conventional and targeted therapies. Immunotherapy represents a developing trend in targeted therapies directed against TNBC and strategies combining immunotherapy and modulators of the DDR pathways are being pursued. There is increasing understanding of the potential interplay between DDR pathways and immune-associated signaling. As such, the question of how we treat TNBC regarding novel immuno-molecular strategies is continually evolving. In this review, we explore the current and upcoming treatment options of TNBC in the context of DNA repair mechanisms and immune-based therapies, with a focus on implications of recent genomic analyses and clinical trial findings.
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spelling doaj.art-8be0f89704b14ba0946bf3868bb2d89f2022-12-21T18:28:34ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.703802703802Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast CancerCurtis A. Clark0Eddy S. Yang1Eddy S. Yang2Eddy S. Yang3Department of Radiation Oncology, University of Alabama at Birmingham (UAB) School of Medicine, Birmingham, AL, United StatesDepartment of Radiation Oncology, University of Alabama at Birmingham (UAB) School of Medicine, Birmingham, AL, United StatesO’Neal Comprehensive Cancer Center, University of Alabama at Birmingham (UAB) School of Medicine, Birmingham, AL, United StatesHugh Kaul Precision Medicine Institute, University of Alabama at Birmingham (UAB) School of Medicine, Birmingham, AL, United StatesTriple-negative breast cancer (TNBC) has poor prognosis with limited treatment options, with little therapeutic progress made during the past several decades. DNA damage response (DDR) associated therapies, including radiation and inhibitors of DDR, demonstrate potential efficacy against TNBC, especially under the guidance of genomic subtype-directed treatment. The tumor immune microenvironment also contributes greatly to TNBC malignancy and response to conventional and targeted therapies. Immunotherapy represents a developing trend in targeted therapies directed against TNBC and strategies combining immunotherapy and modulators of the DDR pathways are being pursued. There is increasing understanding of the potential interplay between DDR pathways and immune-associated signaling. As such, the question of how we treat TNBC regarding novel immuno-molecular strategies is continually evolving. In this review, we explore the current and upcoming treatment options of TNBC in the context of DNA repair mechanisms and immune-based therapies, with a focus on implications of recent genomic analyses and clinical trial findings.https://www.frontiersin.org/articles/10.3389/fonc.2021.703802/fullTNBCDNA repairimmunotherapyPARP inhibition (PARPi)PD-1 - PD-L1 axisDDR (DNA damage response)
spellingShingle Curtis A. Clark
Eddy S. Yang
Eddy S. Yang
Eddy S. Yang
Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer
Frontiers in Oncology
TNBC
DNA repair
immunotherapy
PARP inhibition (PARPi)
PD-1 - PD-L1 axis
DDR (DNA damage response)
title Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer
title_full Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer
title_fullStr Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer
title_full_unstemmed Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer
title_short Harnessing DNA Repair Defects to Augment Immune-Based Therapies in Triple-Negative Breast Cancer
title_sort harnessing dna repair defects to augment immune based therapies in triple negative breast cancer
topic TNBC
DNA repair
immunotherapy
PARP inhibition (PARPi)
PD-1 - PD-L1 axis
DDR (DNA damage response)
url https://www.frontiersin.org/articles/10.3389/fonc.2021.703802/full
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