PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance
The Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular processes, including the regulation of transcription, apoptosis and the DNA damage response. PARP1 possesses Poly (ADP-ribose) activity and when activated by DNA damage, adds branched PAR chains to facilitate the...
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2020-09-01
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doaj-1aaa2df2c5db4cc3a18ff3502771c2762020-11-25T02:31:23ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-09-01810.3389/fcell.2020.564601564601PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor ResistanceMaddison Rose0Joshua T. Burgess1Kenneth O’Byrne2Kenneth O’Byrne3Derek J. Richard4Emma Bolderson5Cancer & Ageing Research Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer & Ageing Research Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer & Ageing Research Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaPrincess Alexandra Hospital, Brisbane, QLD, AustraliaCancer & Ageing Research Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaCancer & Ageing Research Program, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, AustraliaThe Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular processes, including the regulation of transcription, apoptosis and the DNA damage response. PARP1 possesses Poly (ADP-ribose) activity and when activated by DNA damage, adds branched PAR chains to facilitate the recruitment of other repair proteins to promote the repair of DNA single-strand breaks. PARP inhibitors (PARPi) were the first approved cancer drugs that specifically targeted the DNA damage response in BRCA1/2 mutated breast and ovarian cancers. Since then, there has been significant advances in our understanding of the mechanisms behind sensitization of tumors to PARP inhibitors and expansion of the use of PARPi to treat several other cancer types. Here, we review the recent advances in the proposed mechanisms of action of PARPi, biomarkers of the tumor response to PARPi, clinical advances in PARPi therapy, including the potential of combination therapies and mechanisms of tumor resistance.https://www.frontiersin.org/article/10.3389/fcell.2020.564601/fullBRCAPARP inhibitorsDNA damageDNA repaircancertargeted therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maddison Rose Joshua T. Burgess Kenneth O’Byrne Kenneth O’Byrne Derek J. Richard Emma Bolderson |
spellingShingle |
Maddison Rose Joshua T. Burgess Kenneth O’Byrne Kenneth O’Byrne Derek J. Richard Emma Bolderson PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance Frontiers in Cell and Developmental Biology BRCA PARP inhibitors DNA damage DNA repair cancer targeted therapy |
author_facet |
Maddison Rose Joshua T. Burgess Kenneth O’Byrne Kenneth O’Byrne Derek J. Richard Emma Bolderson |
author_sort |
Maddison Rose |
title |
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance |
title_short |
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance |
title_full |
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance |
title_fullStr |
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance |
title_full_unstemmed |
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance |
title_sort |
parp inhibitors: clinical relevance, mechanisms of action and tumor resistance |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2020-09-01 |
description |
The Poly (ADP-ribose) polymerase (PARP) family has many essential functions in cellular processes, including the regulation of transcription, apoptosis and the DNA damage response. PARP1 possesses Poly (ADP-ribose) activity and when activated by DNA damage, adds branched PAR chains to facilitate the recruitment of other repair proteins to promote the repair of DNA single-strand breaks. PARP inhibitors (PARPi) were the first approved cancer drugs that specifically targeted the DNA damage response in BRCA1/2 mutated breast and ovarian cancers. Since then, there has been significant advances in our understanding of the mechanisms behind sensitization of tumors to PARP inhibitors and expansion of the use of PARPi to treat several other cancer types. Here, we review the recent advances in the proposed mechanisms of action of PARPi, biomarkers of the tumor response to PARPi, clinical advances in PARPi therapy, including the potential of combination therapies and mechanisms of tumor resistance. |
topic |
BRCA PARP inhibitors DNA damage DNA repair cancer targeted therapy |
url |
https://www.frontiersin.org/article/10.3389/fcell.2020.564601/full |
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