Elsevier

Redox Biology

Volume 25, July 2019, 101084
Redox Biology

ROS and the DNA damage response in cancer

https://doi.org/10.1016/j.redox.2018.101084Get rights and content
Under a Creative Commons license
open access

Abstract

Reactive oxygen species (ROS) are a group of short-lived, highly reactive, oxygen-containing molecules that can induce DNA damage and affect the DNA damage response (DDR). There is unequivocal pre-clinical and clinical evidence that ROS influence the genotoxic stress caused by chemotherapeutics agents and ionizing radiation. Recent studies have provided mechanistic insight into how ROS can also influence the cellular response to DNA damage caused by genotoxic therapy, especially in the context of Double Strand Breaks (DSBs). This has led to the clinical evaluation of agents modulating ROS in combination with genotoxic therapy for cancer, with mixed success so far. These studies point to context dependent outcomes with ROS modulator combinations with Chemotherapy and radiotherapy, indicating a need for additional pre-clinical research in the field. In this review, we discuss the current knowledge on the effect of ROS in the DNA damage response, and its clinical relevance.

Abbreviation

AML
Acute myeloid leukemia
ATM
Ataxia telangiectasia mutated
ATR
Ataxia telangiectasia mutated and Rad3 related
ATRIP
ATR interacting protein
BSO
Buthionine sulfoximine
BER
Base excision repair
Cdc25
Cell division cycle 25
DDR
DNA damage response
DNA PK
DNA-dependent protein kinase
dNTP
deoxyribonucleotide triphosphate
DSB
Double strand break
ETC
Electron transport chain
H2O2
Hydrogen peroxide
HER-2
human epidermal growth factor receptor 2
HR
Homologous recombination
ICD
Immunogenic cell death
MAPK
Mitogen-activated protein kinases
Mdm2
Mouse double minute 2
MRN
Mre11-Rad50-Nbs1
mtROS
Mitochondrial ROS
NADPH
Nicotinamide adenine dinucleotide phosphate
NCF2
Neutrophil Cytosolic Factor 2
NHEJ
Non-homologous end joining
NRF-2
Nuclear factor (erythroid-derived 2)-like 2
OXPHOS
Oxidative phosphorylation
PLK1
Polo-like kinase 1
PPP
Pentose phosphate pathway
ROS
Reactive oxygen species
RPA
Replication protein A
SOD
Superoxide dismutase
XRCC4
X-ray repair cross-complementing protein 4

Keywords

Reactive Oxygen Species
ROS
DNA damage response
DDR
Chemotherapy
Radiotherapy

Cited by (0)

1

Equal contributions.