ROS and the DNA damage response in cancer
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The most frequently occurring mutations in the tumor suppressor gene TP53 in lung cancer are Guanine → Thymine and Guanine → Adenine transversions.
“The most frequently occurring mutations in the tumor suppressor gene TP53 in lung cancer are Guanine → Thymine and Guanine → Adenine transversions (Srinivas et al. 2019; Gibbons et al. 2014).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Srinivas et al. 2019
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 1× · see citing works
“p53 is a well-studied tumor suppressor that is mutated in over 50% of all cancers [87,88], and affects multiple cellular responses to DNA U.”
BackgroundDNA double-stranded breaks induce histone H2AX phosphorylation on serine 139
Rogakou, E. P., Pilch, D. R., Orr, A. H., Ivanova, V. S., & Bonner, W. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5858 · Cited by 5,438 · see citing works
(1994) · New England Journal of Medicine · doi:10.1056/nejm199404143301501 · Cited by 4,737 · see citing works
The DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368 · cited 1× · see citing works
“This response includes DNA damage recognition, activation of checkpoints, cell cycle arrest, and eventually final outcomes of repair, apoptosis and immune clearance [4,5].”
BackgroundRadiobiology for the Radiologist.
(1974) · Annals of Internal Medicine · doi:10.7326/0003-4819-80-3-438_1 · Cited by 3,498 · see citing works
Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317 · cited 1× · see citing works
“Depending on the nature of the lesion in DNA, specific pathways are activated to facilitate identification of the damaged regions and their repair [2,3].”
BackgroundImmunogenic Cell Death in Cancer Therapy
Kroemer, G., Galluzzi, L., Kepp, O., & Zitvogel, L. (2013) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032712-100008 · Cited by 3,303 · cited 1× · see citing works
“to eventual T-cell mediated killing [116].”
Yang, Y., Li, S., Yang, Q., Shi, Y., Zheng, M., Liu, Y., Chen, F., Song, G., Xu, H., Wan, T., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358696 · Cited by 3,262 · see citing works
ATM and ATR Substrate Analysis Reveals Extensive Protein Networks Responsive to DNA Damage
Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R., Hurov, K. E., Luo, J., Bakalarski, C. E., Zhao, Z., Solimini, N., Lerenthal, Y., et al. (2007) · Science · doi:10.1126/science.1140321 · Cited by 3,075 · see citing works
Association of reactive oxygen species levels and radioresistance in cancer stem cells
Diehn, M., Cho, R. W., Lobo, N. A., Kalisky, T., Dorie, M. J., Kulp, A. N., Qian, D., Lam, J. S., Ailles, L. E., Wong, M., et al. (2009) · Nature · doi:10.1038/nature07733 · Cited by 2,555 · see citing works
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., & Bonner, W. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00610-2 · Cited by 2,098 · cited 1× · see citing works
“Phosphorylated H2AX (γH2AX) helps to recruit multiple components of the DDR to the site of DNA DSBs to initiate DNA DSB repair [58,59].”
BackgroundCauses and consequences of replication stress
Zeman, M. K., & Cimprich, K. A. (2014) · Nature Cell Biology · doi:10.1038/ncb2897 · Cited by 2,079 · cited 2× · see citing works
“physical obstacles to the replication fork [29].”
BackgroundTIGAR, a p53-Inducible Regulator of Glycolysis and Apoptosis
Bensaad, K., Tsuruta, A., Selak, M. A., Vidal, M. N. C., Nakano, K., Bartrons, R., Gottlieb, E., & Vousden, K. H. (2006) · Cell · doi:10.1016/j.cell.2006.05.036 · Cited by 2,019 · see citing works
Ros and ros-mediated cellular signaling
Zhang, J., Wang, X., Vikash, V., Ye, Q., Wu, D., Liu, Y., & Dong, W. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/4350965 · Cited by 1,980 · cited 1× · see citing works
“g·H2O2 regulating NFκB, MAPK pathways) [11].”
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response
Blackford, A. N., & Jackson, S. P. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.015 · Cited by 1,953 · see citing works
An Oncogene-Induced DNA Damage Model for Cancer Development
Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008) · Science · doi:10.1126/science.1140735 · Cited by 1,851 · see citing works
The DNA damage response and cancer therapy
Lord, C. J., & Ashworth, A. (2012) · Nature · doi:10.1038/nature10760 · Cited by 1,843 · cited 1× · see citing works
“The response to DSBs is particularly relevant in carcinogenesis and cancer therapy, as many of the components of the pathway are mutated in cancer, and most current cancer treatment (chemotherapy and radiotherapy) exploits these defects [8].”
BackgroundFree Radicals in Biology: Oxidative Stress and the Effects of Ionizing Radiation
Riley, P. A. (1994) · International Journal of Radiation Biology · doi:10.1080/09553009414550041 · Cited by 1,453 · see citing works
Genomic Instability in Mice Lacking Histone H2AX
Celeste, A., Petersen, S., Romanienko, P. J., Fernandez-Capetillo, O., Chen, H. T., Sedelnikova, O. A., Reina-San-Martin, B., Coppola, V., Meffre, E., Difilippantonio, M. J., et al. (2002) · Science · doi:10.1126/science.1069398 · Cited by 1,385 · see citing works
The antioxidant function of the p53 tumor suppressor
Sablina, A. A., Budanov, A. V., Ilyinskaya, G. V., Agapova, L. S., Kravchenko, J. E., & Chumakov, P. M. (2005) · Nature Medicine · doi:10.1038/nm1320 · Cited by 1,110 · cited 1× · see citing works
“With lower ROS intensity, p53 activates antioxidant genes, while with higher ROS intensity it switches on pro-oxidant genes [93].”
BackgroundDynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
Polo, S. E., & Jackson, S. P. (2011) · Genes & Development · doi:10.1101/gad.2021311 · Cited by 1,092 · see citing works
DNA repair dysregulation from cancer driver to therapeutic target
Curtin, N. J. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3399 · Cited by 1,051 · cited 1× · see citing works
“DNA can be damaged by a variety of exogenous and endogenous insults including chemicals, radiation, free radicals, and topological changes, each causing distinct forms of damage [1].”
BackgroundH2AX: the histone guardian of the genome
Fernández-Capetillo, Ó., Lee, A., Nussenzweig, M. C., & Nussenzweig, A. (2004) · DNA repair · doi:10.1016/j.dnarep.2004.03.024 · Cited by 1,001 · cited 1× · see citing works
“Histone H2AX is another chromatin factor that has been extensively studied in the DNA damage response [57].”
BackgroundEndogenous HMGB1 regulates autophagy
Tang, D., Kang, R., Livesey, K. M., Cheh, C.-W., Farkas, A., Loughran, P., Hoppe, G., Bianchi, M. E., Tracey, K. J., Zeh, H. J., et al. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200911078 · Cited by 951 · see citing works
Yang, H., Hreggvidsdottir, H. S., Palmblad, K., Wang, H., Ochani, M., Li, J., Lü, B., Chavan, S. S., Rosas‐Ballina, M., Al‐Abed, Y., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003893107 · Cited by 812 · see citing works
Respiratory burst in human neutrophils
Dahlgren, C., & Karlsson, A. (1999) · Journal of Immunological Methods · doi:10.1016/s0022-1759(99)00146-5 · Cited by 810 · cited 1× · see citing works
“oxidative bursts in phagocytes to eliminate pathogens) [10] to acting as”
BackgroundMarullo, R., Werner, E., Degtyareva, N., Moore, B., Altavilla, G., Ramalingam, S. S., & Doetsch, P. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081162 · Cited by 777 · cited 1× · see citing works
“In addition to generating nuclear DNA adducts, platinum drugs increase mtROS via formation of mitochondrial DNA adducts [104–106], the extent of which correlates with cytotoxicity [24,107].”
BackgroundChemotherapy-Associated Oxidative Stress: Impact on Chemotherapeutic Effectiveness
Conklin, K. A. (2004) · Integrative Cancer Therapies · doi:10.1177/1534735404270335 · Cited by 752 · see citing works
Free Radicals in Biological Materials
Commoner, B., Townsend, J., & Pake, G. E. (1954) · Nature · doi:10.1038/174689a0 · Cited by 743 · cited 1× · see citing works
“Reactive oxygen species (ROS) comprise of a family of short-lived molecules like O2, H2O2 and •OH, first described in skeletal muscle as free radicals [9].”
BackgroundGupta, S. C., Hevia, D., Patchva, S., Park, B., Koh, W., & Aggarwal, B. B. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4414 · Cited by 736 · see citing works
Shibata, T., Ohta, T., Tong, K. I., Kokubu, A., Odogawa, R., Tsuta, K., Asamura, H., Yamamoto, M., & Hirohashi, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806268105 · Cited by 728 · cited 2× · see citing works
“Decreased Keap1-Nrf2 interaction [111,112] and loss-of-function mutations of Keap1 [112,113] lead to aberrant Nrf2 activation, and therefore resistance to radiotherapy.”
BackgroundMutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release
Venereau, E., Casalgrandi, M., Schiraldi, M., Antoine, D. J., Cattaneo, A., De Marchis, F., Liu, J., Antonelli, A., Preti, A., Raeli, L., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120189 · Cited by 720 · see citing works
CDC25 phosphatases in cancer cells: key players? Good targets?
Boutros, R., Lobjois, V., & Ducommun, B. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2169 · Cited by 710 · see citing works
Schiraldi, M., Raucci, A., Martínez‐Muñoz, L., Livoti, E., Celona, B., Vénéreau, E., Apuzzo, T., Marchis, F. D., Pedotti, M., Bachi, A., et al. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20111739 · Cited by 676 · see citing works
Role of peroxisomes in ros/rns-metabolism: Implications for human disease
Fransen, M., Nordgren, M., Wang, B., & Apanasets, O. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.12.001 · Cited by 644 · cited 1× · see citing works
“polyamine oxidase) [14], (iv) Endoplasmic reticulum (produce H2O2 as a byproduct during protein folding); or upon exposure to exogenous stress like ionizing radiation (IR), chemotherapeutic drugs and environmental insults, which affect the organelles and enzymes listed above [15].”
BackgroundLoss of Keap1 Function Activates Nrf2 and Provides Advantages for Lung Cancer Cell Growth
Ohta, T., Iijima, K., Miyamoto, M., Nakahara, I., Tanaka, H., Ohtsuji, M., Suzuki, T., Kobayashi, A., Yokota, J., Sakiyama, T., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5003 · Cited by 630 · see citing works
Kazama, H., Ricci, J.-E., Herndon, J. M., Hoppe, G., Green, D. R., & Ferguson, T. A. (2008) · Immunity · doi:10.1016/j.immuni.2008.05.013 · Cited by 627 · cited 1× · see citing works
“cells has however been reported to also mediate immunological tolerance [125], although the relevance of this finding to ICD after chemotherapy is unclear.”
BackgroundTsung, A., Klune, J. R., Zhang, X., Jeyabalan, G., Cao, Z., Peng, X., Stolz, D. B., Geller, D. A., Rosengart, M. R., & Billiar, T. R. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070247 · Cited by 616 · cited 1× · see citing works
“The antioxidant N-acetylcysteine attenuates HMGB1 release [121], and HMGB1 release in itself increases ROS production [122], which can lead to further oxidation of HMGB1.”
BackgroundThe DNA Damage Response: Implications for Tumor Responses to Radiation and Chemotherapy
Goldstein, M., & Kastan, M. B. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-081313-121208 · Cited by 590 · cited 2× · see citing works
“Depending on the nature of the lesion in DNA, specific pathways are activated to facilitate identification of the damaged regions and their repair [2,3].”
BackgroundReactive Oxygen Species (ROS)––Induced genetic and epigenetic alterations in human carcinogenesis
Ziech, D., Franco, R., Pappa, A., & Panayiotidis, M. I. (2011) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2011.02.015 · Cited by 568 · cited 1× · see citing works
“polyamine oxidase) [14], (iv) Endoplasmic reticulum (produce H2O2 as a byproduct during protein folding); or upon exposure to exogenous stress like ionizing radiation (IR), chemotherapeutic drugs and environmental insults, which affect the organelles and enzymes listed above [15].”
BackgroundThe structural biochemistry of the superoxide dismutases
Perry, J. J. P., Shin, D. S., Getzoff, E. D., & Tainer, J. A. (2009) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2009.11.004 · Cited by 563 · cited 1× · see citing works
“ROS are produced endogenously by (i) mitochondria (where O2 acts as a terminal electron acceptor for electron transport chain) [12], (ii) NADPH oxidase, a cell membrane bound enzyme [13], (iii) Peroxisomes (which contain enzymes that produce H2O2 e.”
BackgroundOxidative stress induces degradation of mitochondrial DNA
Shokolenko, I. N., Venediktova, N. I., Bochkareva, A., Wilson, G. L., & ALEXEYEV, M. F. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp100 · Cited by 556 · cited 1× · see citing works
“ROS accumulation also induces mitochondrial DNA lesions, strand breaks and degradation of mitochondrial DNA [27].”
BackgroundIncreased ionizing radiation sensitivity and genomic instability in the absence of histone H2AX
Bassing, C. H., Chua, K. F., Sekiguchi, J., Suh, H., Whitlow, S. R., Fleming, J. C., Monroe, B., Ciccone, D. N., Yan, C. T., Vlasáková, K., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122228699 · Cited by 525 · see citing works
ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors
Shen, J., Peng, Y., Wei, L., Zhang, W., Yang, L., Lan, L., Kapoor, P., Ju, Z., Mo, Q., Shih, I.-M., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0849 · Cited by 522 · see citing works
High speed of fork progression induces DNA replication stress and genomic instability
Maya-Mendoza, A., Moudry, P., Merchut-Maya, J. M., Lee, M., Strauss, R., & Bartek, J. (2018) · Nature · doi:10.1038/s41586-018-0261-5 · Cited by 514 · cited 1× · see citing works
“results in genomic instability and paves the way for tumor development through the accumulation of additional pro-carcinogenic changes [28,30].”
BackgroundMa, Y., Chapman, J., Levine, M., Polireddy, K., Drisko, J., & Chen, Q. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007154 · Cited by 501 · cited 2× · see citing works
“On the other end of the spectrum, due to the diverse effects described above for ROS in activating various DNA damage responses, high ROS is also associated with resistance to chemotherapy [18,136].”
BackgroundShibata, T., Kokubu, A., Gotoh, M., Ojima, H., Ohta, T., Yamamoto, M. P., & Hirohashi, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.06.082 · Cited by 470 · cited 2× · see citing works
“Decreased Keap1-Nrf2 interaction [111,112] and loss-of-function mutations of Keap1 [112,113] lead to aberrant Nrf2 activation, and therefore resistance to radiotherapy.”
BackgroundHMGB1 release and redox regulates autophagy and apoptosis in cancer cells
Tang, D., Kang, R., Cheh, C.-W., Livesey, K. M., Liang, X., Schapiro, N. E., Benschop, R., Sparvero, L. J., Amoscato, A. A., Tracey, K. J., et al. (2010) · Oncogene · doi:10.1038/onc.2010.261 · Cited by 461 · see citing works
ARID1A Mutations in Cancer: Another Epigenetic Tumor Suppressor?
Wu, J. N., & Roberts, C. W. M. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0361 · Cited by 457 · see citing works
Molecular Pathways: The Immunogenic Effects of Platinum-Based Chemotherapeutics
Hato, S. V., Khong, A., de Vries, I. J. M., & Lesterhuis, W. J. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-3141 · Cited by 452 · see citing works
Mechanisms of Oncogene-Induced Replication Stress: Jigsaw Falling into Place
Kotsantis, P., Petermann, E., & Boulton, S. J. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1461 · Cited by 416 · cited 4× · see citing works
“Modulation of replication stress by ROS has clinical implications, with the development of several agents- notably ATR and WEE1 inhibitors, which target replication stress in tumours [28].”
BackgroundInfluentialZabludoff, S., Deng, C., Grondine, M. R., Sheehy, A. M., Ashwell, S., Caleb, B. L., Green, S. A., Haye, H. R., Horn, C. L., Janetka, J. W., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0492 · Cited by 411 · see citing works
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A
Williamson, C. T., Miller, R., Pemberton, H. N., Jones, S. E., Campbell, J., Konde, A., Badham, N., Rafiq, R., Brough, R., Gulati, A., et al. (2016) · Nature Communications · doi:10.1038/ncomms13837 · Cited by 382 · see citing works
Mitochondrial dysfunction in ataxia-telangiectasia
Valentin-Vega, Y. A., MacLean, K. H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F. C., Cleveland, J. L., Green, D. R., & Kastan, M. B. (2012) · Blood · doi:10.1182/blood-2011-08-373639 · Cited by 365 · cited 1× · see citing works
“ATM loss modulates mitochondrial turnover, with an increase in aberrant mitochondria and therefore ROS [40,41].”
BackgroundARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice
Mathur, R., Alver, B., Roman, A. K. S., Wilson, B. G., Wang, X., Agoston, A. T., Park, P. J., Shivdasani, R. A., & Roberts, C. W. M. (2016) · Nature Genetics · doi:10.1038/ng.3744 · Cited by 356 · see citing works
p53 Suppresses the Nrf2-dependent Transcription of Antioxidant Response Genes
Faraonio, R., Vergara, P., Marzo, D. D., Pierantoni, G. M., Napolitano, M., Russo, T., & Cimino, F. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605707200 · Cited by 350 · cited 6× · see citing works
“Decreased Keap1-Nrf2 interaction [111,112] and loss-of-function mutations of Keap1 [112,113] lead to aberrant Nrf2 activation, and therefore resistance to radiotherapy.”
BackgroundInfluentialInfluence of Induced Reactive Oxygen Species in p53-Mediated Cell Fate Decisions
Macip, S., Igarashi, M., Berggren, P., Yu, J., Lee, S. W., & Aaronson, S. A. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8576-8585.2003 · Cited by 331 · cited 1× · see citing works
“Furthermore, ROS accumulation has different effects on cell fate depending on p53 status; with more apoptosis in cells with functional WT p53 [92].”
Backgrounddos Santos, N. A. G., Bezerra, C. S. C., Martins, N. M., Curti, C., Bianchi, M. L. P., & dos Santos, A. C. (2007) · Archives of Toxicology · doi:10.1007/s00204-006-0173-2 · Cited by 329 · see citing works
Cisplatin induced Mitochondrial DNA damage in dorsal root ganglion neurons
Podratz, J. L., Knight, A. M., Ta, L. E., Staff, N. P., Gass, J. M., Genelin, K., Schlattau, A., Lathroum, L., & Windebank, A. J. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.11.017 · Cited by 322 · see citing works
Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy
Marengo, B., Nitti, M., Furfaro, A. L., Colla, R., Ciucis, C. D., Marinari, U. M., Pronzato, M. A., Traverso, N., & Domenicotti, C. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/6235641 · Cited by 319 · cited 1× · see citing works
“Secondly, ROS has a dose dependent effect on activity of proteins leading to differential downstream outcomes [140], which are”
BackgroundDNA damage induces reactive oxygen species generation through the H2AX-Nox1/Rac1 pathway
Kang, M. A., So, E.-Y., Simons, A. L., Spitz, D. R., & Ouchi, T. (2012) · Cell Death & Disease · doi:10.1038/cddis.2011.134 · Cited by 311 · see citing works
ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death
Garg, A. D., Dudek, A. M., Ferreira, G. B., Verfaillie, T., Vandenabeele, P., Krysko, D. V., Mathieu, C., & Agostinis, P. (2013) · Autophagy · doi:10.4161/auto.25399 · Cited by 305 · cited 1× · see citing works
“Induction of autophagy via increased levels of ROS results in biochemical hallmarks of ICD evasion [130].”
BackgroundThe Superoxide-Generating Oxidase Nox1 Is Functionally Required for Ras Oncogene Transformation
Mitsushita, J., Lambeth, J., & Kamata, T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3909 · Cited by 302 · cited 1× · see citing works
“γH2AX mediated activation of the Nox1-Rac1 complex [67,68] regulates ROS production [69].”
BackgroundHemorrhagic Shock Induces NAD(P)H Oxidase Activation in Neutrophils: Role of HMGB1-TLR4 Signaling
Fan, J., Li, Y., Levy, R. M., Fan, J., Hackam, D. J., Vodovotz, Y., Yang, H., Tracey, K. J., Billiar, T. R., & Wilson, M. A. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.10.6573 · Cited by 300 · cited 1× · see citing works
“The antioxidant N-acetylcysteine attenuates HMGB1 release [121], and HMGB1 release in itself increases ROS production [122], which can lead to further oxidation of HMGB1.”
BackgroundNox1-dependent Reactive Oxygen Generation Is Regulated by Rac1*
Cheng, G.-J., Diebold, B., Hughes, Y., & Lambeth, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512751200 · Cited by 288 · cited 1× · see citing works
“γH2AX mediated activation of the Nox1-Rac1 complex [67,68] regulates ROS production [69].”
BackgroundChoi, Y.-M., Kim, H., Shim, W., Anwar, M. A., Kwon, J.-W., Kwon, H., Kim, H. J., Jeong, H., Kim, H. M., Hwang, D., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135083 · Cited by 283 · see citing works
Monti, D., Mitchell, E. P., Bazzan, A. J., Littman, S. J., Zabrecky, G. P., Yeo, C. J., Pillai, M. V., Newberg, A. B., Deshmukh, S., & Levine, M. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029794 · Cited by 270 · see citing works
Yang, Z., Schumaker, L. M., Egorin, M. J., Zuhowski, E. G., Guo, Z., & Cullen, K. J. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-1037 · Cited by 270 · see citing works
Lissanu, Y., Sun, Y., Terranova, C. J., Khan, F., Martínez-Ledesma, E., Gay, J. P., Gao, G., Mullinax, R. A., Khor, T. O., Feng, N., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0019-5 · Cited by 262 · see citing works
Mechanism of p53 stabilization by ATM after DNA damage
Cheng, Q., & Chen, J. (2010) · Cell Cycle · doi:10.4161/cc.9.3.10556 · Cited by 248 · cited 1× · see citing works
“Upon cellular stress and DNA damage; p53 is stabilized and aids in transcription of genes to determine cell fate [89].”
BackgroundGeneration and Function of Reactive Oxygen Species in Dendritic Cells During Antigen Presentation
Matsue, H., Edelbaum, D., Shalhevet, D., Mizumoto, N., Yang, C., Mummert, M. E., Oeda, J., Masayasu, H., & Takashima, A. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.6.3010 · Cited by 247 · cited 1× · see citing works
“ROS plays an active role in the pathways involved in immunogenic cell death including the induction of autophagy [127], and antigen presentation by immune cells [128,129].”
BackgroundShi, Y., Nikulenkov, F., Zawacka‐Pankau, J., Li, H., Gabdoulline, R. R., Xu, J., Eriksson, S. E., Hedström, E., Issaeva, N., Kel, A. E., et al. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2013.186 · Cited by 232 · see citing works
NADPH Oxidases: A Perspective on Reactive Oxygen Species Production in Tumor Biology
Meitzler, J. L., Antony, S., Wu, Y., Juhasz, A. N., Liu, H., Jiang, G., Lu, J., Roy, K., & Doroshow, J. H. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5603 · Cited by 205 · cited 1× · see citing works
“ROS are produced endogenously by (i) mitochondria (where O2 acts as a terminal electron acceptor for electron transport chain) [12], (ii) NADPH oxidase, a cell membrane bound enzyme [13], (iii) Peroxisomes (which contain enzymes that produce H2O2 e.”
BackgroundXiao, D., Herman-Antosiewicz, A., Antosiewicz, J., Xiao, H., Brisson, M., Lazo, J. S., & Singh, S. V. (2005) · Oncogene · doi:10.1038/sj.onc.1208759 · Cited by 199 · see citing works
Redox-sensitive alteration of replisome architecture safeguards genome integrity
Somyajit, K., Gupta, R., Polášek-Sedláčková, H., Neelsen, K. J., Ochs, F., Rask, M., Choudhary, C., & Lukas, J. (2017) · Science · doi:10.1126/science.aao3172 · Cited by 190 · cited 1× · see citing works
“Elevated ROS lead to dissociation of PRDX2 and TIMELESS, thus slowing replication fork speed [36].”
BackgroundRedox Regulation of p53, Redox Effectors Regulated by p53: A Subtle Balance
Maillet, A., & Pervaiz, S. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4434 · Cited by 187 · see citing works
Reciprocal down-regulation of p53 and SOD2 gene expression-implication in p53 mediated apoptosis
Drane, P., Bravard, A., Bouvard, V., & May, E. (2001) · Oncogene · doi:10.1038/sj.onc.1204101 · Cited by 180 · cited 2× · see citing works
“Furthermore, under conditions of high ROS, p53 has been demonstrated to downregulate antioxidant proteins including SOD2 [97] and the anti-oxidant transcriptional factor Nrf2 [98].”
BackgroundGruosso, T., Mieulet, V., Cardon, M., Bourachot, B., Kieffer, Y., Devun, F., Dubois, T., Dutreix, M., Vincent‐Salomon, A., Miller, K. M., et al. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201505891 · Cited by 179 · see citing works
Teng, Y., Yadav, T., Duan, M.-H., Tan, J. J., Xiang, Y., Gao, B., Xu, J., Liang, Z., Liu, Y., Nakajima, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-06586-3 · Cited by 179 · see citing works
Maya‐Mendoza, A., Ostráková, J., Košař, M., Hall, A., Dušková, P., Mistrík, M., Merchut‐Maya, J. M., Hodný, Z., Bártková, J., Christensen, C., et al. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.11.001 · Cited by 170 · see citing works
Redox Modulation of HMGB1-Related Signaling
Janko, C., Filipović, M. R., Munoz, L. E., Schorn, C., Schett, G. A., Ivanović‐Burmazović, I., & i, M. H. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5179 · Cited by 166 · see citing works
Wanka, C., Steinbach, J., & Rieger, J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.384578 · Cited by 165 · see citing works
Redox Regulation of Human OGG1 Activity in Response to Cellular Oxidative Stress
Bravard, A., Vacher, M., Gouget, B., Coutant, A., de Boisferon, F. H., Marsin, S., Chevillard, S., & Radicella, J. P. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00624-06 · Cited by 165 · see citing works
Mehta, M. P., Shapiro, W. R., Phan, S. C., Gervais, R., Carrié, C., Chabot, P., Patchell, R. A., Glantz, M., Recht, L. D., Langer, C. J., et al. (2008) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2008.05.068 · Cited by 163 · see citing works
Salehi, F., Behboudi, H., Kavoosi, G., & Ardestani, S. K. (2018) · Scientific Reports · doi:10.1038/s41598-018-32308-2 · Cited by 157 · cited 1× · see citing works
“formation of 8-oxo guanine) [25], which can lead to G-T or G-A transversions if unrepaired.”
BackgroundPolireddy, K., Dong, R., Reed, G. A., Yu, J., Chen, P., Williamson, S. K., Violet, P.-C., Pessetto, Z. Y., Godwin, A. K., Fan, F., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-17568-8 · Cited by 153 · see citing works
Regulation of Cellular Metabolism and Hypoxia by p53Preprint
Humpton, T. J., & Vousden, K. H. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026146 · Cited by 147 · cited 2× · see citing works
“p53 is a redox protein with clusters of cysteine residues that can be targets of ROS [90], but it can also regulate ROS in turn [91].”
BackgroundLocus-specific mutation databases: pitfalls and good practice based on the p53 experience
Soussi, T., Ishioka, C., Claustres, M., & Béroud, C. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1783 · Cited by 144 · cited 1× · see citing works
“p53 is a well-studied tumor suppressor that is mutated in over 50% of all cancers [87,88], and affects multiple cellular responses to DNA U.”
BackgroundMa, X., Wang, L., Huang, D., Li, Y., Yang, D., Li, T., Li, F., Sun, L., Wei, H., He, K., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01647-5 · Cited by 140 · see citing works
Ju, H.-Q., Gocho, T., Aguilar, M., Wu, M., Zhuang, Z.-N., Fu, J., Yanaga, K., Huang, P., & Chiao, P. J. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-14-0420 · Cited by 137 · see citing works
Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later
González, M. J., Miranda-Massari, J. R., Mora, E., Guzmán, A., Riordan, N. H., Riordan, H. D., Casciari, J. J., Jackson, J. A., & Román‐Franco, A. A. (2005) · Integrative Cancer Therapies · doi:10.1177/1534735404273861 · Cited by 136 · cited 1× · see citing works
“This has led to suggestions that ROS modulators could be used for cancer primary prevention, or to enhance therapeutic responses [18,19].”
BackgroundJiang, Y., Guo, C., Vasko, M. R., & Kelley, M. R. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1173 · Cited by 130 · see citing works
Alexander, M. S., Wilkes, J. G., Schroeder, S. R., Buettner, G. R., Wagner, B. A., Du, J., Gibson-Corley, K. N., O’Leary, B. R., Spitz, D. R., Buatti, J. M., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1680 · Cited by 129 · see citing works
Novel signaling axis for ROS generation during K-Ras-induced cellular transformation
Park, M.-T., Kim, M.-J., Suh, Y., Kim, R.-K., Kim, H., Lim, E.-J., Yoo, K.-C., Lee, G.-H., Kim, Y.-H., Hwang, S.-G., et al. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.34 · Cited by 126 · see citing works
Nrf2 is a potential therapeutic target in radioresistance in human cancer
Zhou, S., Ye, W., Shao, Q., Zhang, M., & Liang, J. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.09.001 · Cited by 115 · cited 1× · see citing works
“ATM-deficient cells also have increased ROS due to defects in NRF2 activity, a transcriptional factor which promotes the expression of antioxidant proteins under conditions of cellular stress [42,43].”
BackgroundBryant, C., Rawlinson, R., & Massey, A. J. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-570 · Cited by 114 · see citing works
Oxidative stress induces H2AX phosphorylation in human spermatozoa
Li, Z., Yang, J. J., & Huang, H. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.016 · Cited by 112 · cited 1× · see citing works
“Conversely, acute oxidative stress increases γH2AX activation and DDR signaling [63].”
BackgroundMontero, A. J., Diaz-Montero, C. M., Deutsch, Y. E., Hurley, J. E., Koniaris, L. G., Rumboldt, T., Yasir, S., Jorda, M., Garret-Mayer, E., Avisar, E., et al. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1889-0 · Cited by 112 · see citing works
Zhang, Z., Hou, X., Shao, C., Li, J., Cheng, J., Kuang, S., Ahmad, N., Ratliff, T. L., & Liu, X. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1916 · Cited by 109 · see citing works
Systematic Review of Intravenous Ascorbate in Cancer Clinical Trials
Nauman, G., Gray, J. C., Parkinson, R., Levine, M., & Paller, C. J. (2018) · Antioxidants · doi:10.3390/antiox7070089 · Cited by 107 · cited 1× · see citing works
“[137], and further RCTs are required to determine the efficacy of these strategies.”
BackgroundATM/G6PD-driven redox metabolism promotes FLT3 inhibitor resistance in acute myeloid leukemia
Gregory, M. A., D’Alessandro, A., Calderon, F. A., Kim, J., Nemkov, T. G., Adane, B., Rozhok, A. I., Kumar, A., Kumar, V., Pollyea, D. A., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1603876113 · Cited by 106 · see citing works
APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress
Willis, J., Patel, Y., Lentz, B. L., & Yan, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301445110 · Cited by 100 · cited 7× · see citing works
“Chk1 inhibition potentiates the cytotoxic effects of DNA-damage therapeutics in preclinical studies [75–77], although the relevance of ROS in this context has not been clearly defined.”
BackgroundInfluentialWang, S., Chen, M.-S., Chou, Y., Ueng, Y., Yin, P., Yeh, T.-S., & Lee, H. (2016) · Oncotarget · doi:10.18632/oncotarget.12356 · Cited by 93 · see citing works
Reactive oxygen species are essential mediators in antigen presentation by Kupffer cells
Maemura, K., Zheng, Q., Wada, T., Ozaki, M., Takao, S., Aikou, T., Bulkley, G. B., Klein, A. S., & Sun, Z. (2005) · Immunology and Cell Biology · doi:10.1111/j.1440-1711.2005.01323.x · Cited by 90 · cited 1× · see citing works
“ROS plays an active role in the pathways involved in immunogenic cell death including the induction of autophagy [127], and antigen presentation by immune cells [128,129].”
BackgroundKozlov, S., Waardenberg, A. J., Engholm‐Keller, K., Arthur, J. W., Graham, M. E., & Lavin, M. F. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.055723 · Cited by 89 · cited 1× · see citing works
“directly activated by oxidative stress, for example by H2O2, leading to its autophosphorylation and subsequent downstream activation of the DDR pathway [47].”
BackgroundGuerriero, J. L., Ditsworth, D., Catanzaro, J. M., Sabino, G. J., Furie, M. B., Kew, R. R., Crawford, H. C., & Zong, W. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003267 · Cited by 88 · cited 1× · see citing works
“Oxidized HMGB1 enhances apoptosis and chemosensitivity in pancreatic and colorectal cancer cell lines [123], whereas reduced HMGB1 promotes autophagy-mediated chemoresistance towards melphalan, oxaliplatin and paclitaxel [123,124].”
Backgroundde Aguiar, P. H. N., Furtado, C., Repolês, B. M., Ribeiro, G. A., Mendes, I. C., Peloso, E. D. F., Gadelha, F. R., Macedo, A. M., Franco, G. R., Pena, S. D. J., et al. (2013) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002279 · Cited by 88 · see citing works
Katsube, T., Mori, M., Tsuji, H., Shiomi, T., Wang, B., Liu, Q., Nenoi, M., & Onoda, M. (2014) · The Journal of Biochemistry · doi:10.1093/jb/mvu021 · Cited by 87 · cited 1× · see citing works
“Oxidative stress by H2O2 requires ATR for γ-H2AX accumulation and activation of the DDR [48], as well as ATR dependent phosphorylation of Chk1 [49].”
BackgroundAbdel-Fatah, T. M. A., Middleton, F. K., Arora, A., Agarwal, D., Chen, T., Moseley, P. M., Perry, C., Doherty, R. E., Chan, S. Y. T., Green, A. R., et al. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.10.013 · Cited by 86 · see citing works
Constitutive expression of γ-H2AX has prognostic relevance in triple negative breast cancer
Nagelkerke, A., van Kuijk, S. J. A., Sweep, F. C. G. J., Nagtegaal, I. D., Hoogerbrugge, N., Martens, J. W. M., Timmermans, M. A. M., van Laarhoven, H. W. M., Bussink, J., & Span, P. N. (2011) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2011.07.009 · Cited by 84 · see citing works
Meng, Y., Chen, C., Yung, M. M. H., Sun, W., Sun, J. F., Li, Z., Li, J., Li, Z., Zhou, W., Liu, S. S., et al. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.04.029 · Cited by 77 · see citing works
Wright, M. E., Virtamo, J. R. K., Hartman, A. M., Pietinen, P., Edwards, B. K., Taylor, P. R., Huttunen, J. K., & Albanes, D. (2007) · Cancer · doi:10.1002/cncr.22482 · Cited by 70 · see citing works
Cannan, W. J., Tsang, B. P., Wallace, S. S., & Pederson, D. S. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.571588 · Cited by 68 · cited 9× · see citing works
“As 8- Oxo-dG can be potentially converted to DSBs, further work will be required to understand the contribution of ROS to DSB generation through this route.”
BackgroundInfluentialStrategies for Prolonged Therapy in Patients With Advanced Non–Small-Cell Lung Cancer
Fidias, P. M., & Novello, S. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.30.7074 · Cited by 68 · see citing works
Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells
Chen, S., Chen, X., Xie, G., He, Y., Yan, D., Zheng, D., Li, S., Fu, X., Li, Y., Pang, X., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.9616 · Cited by 68 · see citing works
Manipulating DNA damage-response signaling for the treatment of immune-mediated diseases
McNally, J. P., Millen, S. H., Chaturvedi, V., Lakes, N., Terrell, C. E., Elfers, E. E., Carroll, K. R., Hogan, S. P., Andreassen, P. R., Kanter, J., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703683114 · Cited by 62 · see citing works
Chang, M., Lin, L., Wu, M.-T., Chan, C., Chang, H., Lee, M., Sun, T.-Y., Jeng, P., Yeung, S., Lin, H.-J., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0143663 · Cited by 59 · see citing works
Vandenberk, L., Garg, A. D., Verschuere, T., Koks, C., Belmans, J., Beullens, M., Agostinis, P., Vleeschouwer, S. D., & Gool, S. V. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1083669 · Cited by 57 · see citing works
Koczor, C. A., Shokolenko, I. N., Boyd, A. K., Balk, S. P., Wilson, G. L., & LeDoux, S. P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.036020 · Cited by 56 · cited 4× · see citing works
“Downstream of the sensor kinases are the transducer kinases Chk2 (activated by ATM) and Chk1 (activated by ATR), which phosphorylate and regulate proteins involved in DDR, DNA repair and cell cycle arrest.”
BackgroundInfluentialBradley, K. A., Zhou, T., McNall‐Knapp, R. Y., Jakacki, R. I., Levy, A., Vézina, G., & Pollack, I. F. (2012) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2012.09.004 · Cited by 55 · see citing works
Okoh, V. O., Garba, N. A., Penney, R. B., Das, J., Deoraj, A., Singh, K. P., Sarkar, S., Felty, Q. H., Yoo, C., Jackson, R. M., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2014.586 · Cited by 54 · see citing works
Temporal DNA-PK activation drives genomic instability and therapy resistance in glioma stem cells.
Wang, Y., Xu, H., Liu, T.-R., Huang, M.-G., Butter, P., Li, C.-S., Zhang, L., Kao, G., Gong, Y.-Q., Maity, A., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.98096 · Cited by 54 · see citing works
Anderson, C., & Reynolds, C. P. (2002) · Bone Marrow Transplantation · doi:10.1038/sj.bmt.1703605 · Cited by 53 · see citing works
Autophagy substrate SQSTM1/p62 regulates chromatin ubiquitination during the DNA damage response
Wang, Y., Zhu, W., & Zhao, Y. (2016) · Autophagy · doi:10.1080/15548627.2016.1245262 · Cited by 52 · cited 1× · see citing works
“In contrast, ROS accumulation inhibits Aurora kinase A [86], even though PLK1 and Aurora-A are epistatic in the pathway.”
BackgroundIndependent Mechanistic Inhibition of Cdc25 Phosphatases by a Natural Product Caulibugulone
Brisson, M., Foster, C. A., Wipf, P., Joo, B., Tomko, R. J., Nguyen, T. P. T., & Lazo, J. S. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.028589 · Cited by 50 · see citing works
He, L., Nan, M.-H., Oh, H. C., Kim, Y. H., Jang, J. H., Erikson, R. L., Ahn, J. S., & Kim, B. Y. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.05.032 · Cited by 49 · see citing works
Giurgiovich, A. J. (1997) · Carcinogenesis · doi:10.1093/carcin/18.1.93 · Cited by 48 · see citing works
Ward, A., & Hudson, J. W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087918 · Cited by 46 · cited 1× · see citing works
“Interestingly, oxidative stress with H2O2 increases PLK1 expression in a p53 dependent manner [84,85], but maintains a G2/M arrest.”
BackgroundMacip, S., Kosoy, A., Lee, S. W., O’Connell, M. J., & Aaronson, S. A. (2006) · Oncogene · doi:10.1038/sj.onc.1209629 · Cited by 45 · see citing works
Itamochi, H., Nishimura, M., Oumi, N., Kato, M., Oishi, T., Shimada, M., Sato, S., Naniwa, J., Sato, S., Kudoh, A., et al. (2013) · International Journal of Gynecological Cancer · doi:10.1097/igc.0000000000000014 · Cited by 44 · see citing works
Kwan, S.-Y., Cheng, X., Tsang, Y. T. M., Choi, J.-S., Kwan, S., Izaguirre, D. I., Kwan, H. S., Gershenson, D. M., & Wong, K. (2016) · Oncotarget · doi:10.18632/oncotarget.10921 · Cited by 44 · cited 1× · see citing works
“ROS lowers ARID1A expression by promoter methylation in ovarian cancers [53,54], and ARID1A loss sensitizes ovarian cancer cells to ROS inducing agent elesclomol [55].”
BackgroundHigh expression of phospho-H2AX predicts a poor prognosis in colorectal cancer.
Lee, Y., Yin, T., Chen, Y., Chai, C., Wang, J., Liu, M.-C., Lin, Y.-C., & Kan, J. (2015) · PubMed · Cited by 43 · see citing works
Sedletska, Y., Radicella, J. P., & Sage, É. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt731 · Cited by 42 · cited 1× · see citing works
“Oxidized bases occurring from ROS activity also present a physical obstacle to replication forks [37], resulting in the breakdown of replication forks at fragile sites across the genome.”
BackgroundZulato, E., Ciccarese, F., Agnusdei, V., Pinazza, M., Nardo, G., Iorio, E., Curtarello, M., Silic‐Benussi, M., Rossi, E. M. C., Venturoli, C., et al. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.019 · Cited by 42 · see citing works
Patwardhan, R. S., Sharma, D., Checker, R., Thoh, M., & Sandur, S. K. (2015) · Free Radical Research · doi:10.3109/10715762.2015.1056180 · Cited by 39 · see citing works
Sullivan, K. D., Palaniappan, V. V., & Espinosa, J. M. (2014) · Cell Cycle · doi:10.4161/15384101.2014.973330 · Cited by 39 · cited 1× · see citing works
“ATM loss modulates mitochondrial turnover, with an increase in aberrant mitochondria and therefore ROS [40,41].”
BackgroundSinglet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication
Graindorge, D., Martineau, S., Machon, C., Arnoux, P., Guitton, J., Francesconi, S., Frochot, C., Sage, É., & Girard, P.-M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140645 · Cited by 38 · cited 1× · see citing works
“ROS oxidize dNTPs to affect polymerase activity and thereby reduce replication fork velocity in vitro [34,35].”
BackgroundWinarto, H., Tan, M. I., Sadikin, M., & Wanandi, S. I. (2017) · Translational Oncogenomics · doi:10.1177/1177272716689818 · Cited by 38 · see citing works
Barr, P. M., Miller, T. P., Friedberg, J. W., Peterson, D. R., Baran, A. M., Herr, M. M., Spier, C. M., Cui, H., Roe, D. J., Persky, D. O., et al. (2014) · Blood · doi:10.1182/blood-2014-04-570044 · Cited by 37 · see citing works
Fan, P., Zhang, Y., Wang, Y., Wei, W., Zhou, Y., Xie, Y., Wang, X., Qi, Y., Chang, L., Jia, Z., et al. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.449 · Cited by 37 · see citing works
Moulder, S. L., Dhillon, N., Ng, C. S., Hong, D. S., Wheler, J. J., Naing, A., Tse, S., LaPaglia, A., Dorr, R. T., Hersh, E. M., et al. (2009) · Investigational New Drugs · doi:10.1007/s10637-009-9273-1 · Cited by 35 · see citing works
Duong, H., Hong, Y. B., Kim, J. S., Lee, H., Yi, Y. W., Kim, Y. J., Wang, A., Zhao, W., Cho, C., Seong, Y., et al. (2013) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12101 · Cited by 33 · see citing works
Xie, H., Chen, P., Hw, H., Lp, L., & Zhao, F. (2017) · PubMed · Cited by 33 · see citing works
William, W. N., Zinner, R., Karp, D. D., Oh, Y. W., Glisson, B. S., Phan, S.-C., & Stewart, D. J. (2007) · Journal of Thoracic Oncology · doi:10.1097/jto.0b013e31811f4719 · Cited by 28 · see citing works
Miura, M., & Sasaki, T. (1991) · Radiation Research · doi:10.2307/3577823 · Cited by 28 · cited 1× · see citing works
“Early studies observed that depletion of GSH could enhance radiosensitivity of squamous cell carcinoma cell lines [110].”
BackgroundLi, M., Lin, Y., Palchik, G. A., Matsunaga, S., Wang, D., & Chen, B. P. C. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.08.019 · Cited by 27 · cited 1× · see citing works
“Similarly, DNA-PK deficient cells accumulate higher ROS upon oxidative stress [45,46].”
BackgroundRole of imaging in predicting response to neoadjuvant chemotherapy in gastric cancer
Kwee, R. M. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i7.1650 · Cited by 25 · cited 1× · see citing works
“have profound effects on both pro-survival and pro-death pathways [138], and may result in attenuation of specific chemotherapeutic responses [139].”
BackgroundChatzimichail, E. A., Matthaios, D., Bouros, D. E., Karakitsos, P., Romanidis, Κ., Kakolyris, S., Papashinopoulos, G., & Rigas, A. G. (2014) · International Journal of Genomics · doi:10.1155/2014/160236 · Cited by 23 · see citing works
Agathanggelou, A., Weston, V., Perry, T., Davies, N. J., Skowrońska, A., Payne, D. T., Fossey, J., Oldreive, C., Wei, W., Pratt, G., et al. (2015) · Haematologica · doi:10.3324/haematol.2014.115170 · Cited by 21 · see citing works
A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer
Cohen, S. J., Zalupski, M. M., Modiano, M., Conkling, P., Patt, Y. Z., Davis, P., Dorr, R. T., Boytim, M. L., & Hersh, E. M. (2009) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-009-1162-y · Cited by 20 · cited 1× · see citing works
“While the pro-oxidant molecule Imexon demonstrated initial promising results in advanced pancreatic cancer in combination with gemcitabine [134], a larger phase II trial demonstrated no significant survival benefit or responses (ClinicalTrials.”
BackgroundNOV-002 plus carboplatin in platinum-resistant ovarian cancer
Krasner, C. N., Seiden, M. V., Penson, R. T., Roche, M. R., Kendall, D. L., Young, J., Matulonis, U. A., Pereira, L., & Berlin, S. T. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.26.15_suppl.5593 · Cited by 9 · see citing works
Fidias, P. M., Ciuleanu, T. A., Gladkov, O. A., Manikhas, G., Bondarenko, I., Pluzanska, A., Ramlau, R., & Lynch, T. J. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.18_suppl.lba7007 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 153 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Reactive oxygen species (ROS) as pleiotropic physiological signalling agents
Sies, H., & Jones, D. P. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0230-3 · Cited by 5,335 · see citing works
Juan, C. A., Pérez de la Lastra, J. M., Plou, F. J., & Pérez-Lebeña, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094642 · Cited by 2,810 · see citing works
“The DNA damage caused by ROS, from endogenous or exogenous sources, has been a significant breakthrough in carcinogenesis research over the last 20 years [22].”
BackgroundReactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Wang, B., Wang, Y., Zhang, J., Hu, C., Jiang, J., Li, Y., & Peng, Z. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03476-6 · Cited by 897 · see citing works
Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances
Xu, X., Pang, Y., & Fan, X. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02253-4 · Cited by 939 · see citing works
The double-edged roles of ROS in cancer prevention and therapy
Wang, Y., Qi, H., Liu, Y., Duan, C., Liu, X., Xia, T., Chen, D., Piao, H., & Liu, H. (2021) · Theranostics · doi:10.7150/thno.56747 · Cited by 646 · see citing works
“Moreover, ROS not only delay the identification of damaged regions by affecting sensor kinases (ATM and ATR) and downstream transducer kinases (CHK1 and CHK2) [101, 102], but also impair the activation of DNA repair enzyme OGG1 by oxidation of critical cysteine residues [103].”
BackgroundCopper uptake, essentiality, toxicity, detoxification and risk assessment in soil-plant environment
Shabbir, Z., Sardar, A., Shabbir, A., Abbas, G., Shamshad, S., Khalid, S., Natasha, N., Murtaza, G., Dumat, C., & Shahid, M. A. R. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.127436 · Cited by 482 · see citing works
ROS: Basic Concepts, Sources, Cellular Signaling, and its Implications in Aging Pathways
de Almeida, A. J. P. O., de Oliveira, J. C. P. L., Pontes, L. V. D. S., Júnior, J. F. D. S., Gonçalves, T. A. F., Dantas, S. H., Feitosa, M. S. D. A., Silva, A. O., & de Medeiros, I. A. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/1225578 · Cited by 521 · see citing works
“Oxidative stress can injure DNA, leading to DNA damage response (DDR) [207].”
The multifaceted role of reactive oxygen species in tumorigenesis
Kirtonia, A., Sethi, G., & Garg, M. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03536-5 · Cited by 452 · see citing works
Anti‐inflammatory hydrogel dressings and skin wound healing
Huang, C., Dong, L., Zhao, B., Lu, Y., Huang, S., Yuan, Z., Luo, G., Xu, Y. X., & Qian, W. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.1094 · Cited by 452 · see citing works
Tumor‐Microenvironment‐Responsive Nanomedicine for Enhanced Cancer Immunotherapy
Peng, S., Xiao, F., Chen, M., & Gao, H. (2021) · Advanced Science · doi:10.1002/advs.202103836 · Cited by 446 · see citing works
ROS induced lipid peroxidation and their role in ferroptosis
Endale, H. T., Tesfaye, W., & Mengstie, T. A. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1226044 · Cited by 423 · see citing works
Interplay of oxidative stress, cellular communication and signaling pathways in cancer
Iqbal, M. J., Kabeer, A., Abbas, Z., Siddiqui, H. A., Călina, D. C., Sharifi‐Rad, J., & Cho, W. C. S. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01398-5 · Cited by 426 · see citing works
“At high oxidative stress levels, p53 promotes cell death by suppressing the expression of antioxidant genes and inducing the expression of prooxidative genes, including PIG3, PIG6, FDRX, Bax, Puma to further stimulate ROS production in cell that leads towards senescence [40, 45–47].”
BackgroundAnti-angiogenic therapy: current challenges and future perspectives
Lopes-Coelho, F., Martins, F., Pereira, S. A., & Serpa, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073765 · Cited by 416 · see citing works
“However, higher ROS are also associated with chemotherapy resistance [221].”
BackgroundDas, A. K. (2023) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2023.165076 · Cited by 384 · see citing works
DNA Damage/Repair Management in Cancers
Alhmoud, J. F., Woolley, J. F., Moustafa, A. A., & Malki, M. I. (2020) · Cancers · doi:10.3390/cancers12041050 · Cited by 378 · see citing works
“Sources of DNA damage can be endogenous or exogenous and include reactive oxygen species (ROS) or ionizing radiation [1].”
BackgroundCellular Stress Responses in Radiotherapy
Kim, W., Lee, S., Seo, D., Kim, D., Kim, K., Kim, E., Kang, J., Seong, K. M., Youn, H., & Youn, B. (2019) · Cells · doi:10.3390/cells8091105 · Cited by 343 · see citing works
Cancer Metabolism: The Role of ROS in DNA Damage and Induction of Apoptosis in Cancer Cells
Zhao, Y., Ye, X., Xiong, Z., Ihsan, A., Arés, I., Martínez, M., López-Torres, B., Martínez‐Larrañaga, M., Anadón, A., Wang, X., et al. (2023) · Metabolites · doi:10.3390/metabo13070796 · Cited by 340 · see citing works
“The imbalance of ROS induces adverse cancer outcomes by affecting sign l transduction wi hin the DDR [93] because the accumulation of ROS can be toxic to cells, and toxic levels of ROS have been shown to affect replication”
BackgroundInfluentialTargeting Metabolic Plasticity and Flexibility Dynamics for Cancer Therapy
Fendt, S., Frezza, C., & Erez, A. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0844 · Cited by 320 · see citing works
Helicobacter pylori and gastric cancer: mechanisms and new perspectives
Duan, Y., Xu, Y., Dou, Y., & Xu, D. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01654-2 · Cited by 311 · see citing works
The Influence of Cell Cycle Regulation on Chemotherapy
Sun, Y., Liu, Y., Ma, X., & Hu, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136923 · Cited by 306 · see citing works
“ROS can induce CHK1 activation or directly affect the protein phosphatase Cdc25 family (Cdc25A, B, and C) to promote cell cycle arrest [98].”
BackgroundThe emerging role of oxidative stress in inflammatory bowel disease
Muro, P., Zhang, L., Li, S., Zhao, Z., Jin, T., Mao, F., & Mao, Z. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1390351 · Cited by 313 · see citing works
“Furthermore, ROS/RNS can directly attack DNA, causing oxidative DNA damage in IBD (41).”
BackgroundMucha, P., Skoczyńska, A., Małecka, M., Hikisz, P., & Budzisz, E. (2021) · Molecules · doi:10.3390/molecules26164886 · Cited by 290 · see citing works
NF‐κB signalling pathways in nucleus pulposus cell function and intervertebral disc degeneration
Zhang, G., Liu, M., Chen, H., Wu, Z., Gao, Y., Ma, Z., He, X., & Kang, X. (2021) · Cell Proliferation · doi:10.1111/cpr.13057 · Cited by 263 · see citing works
Intratumoural microbiota: a new frontier in cancer development and therapy
Cao, Y., Xia, H., Tan, X., Shi, C., Ma, Y., Meng, D., Zhou, M., Lv, Z., Wang, S., & Jin, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01693-0 · Cited by 263 · see citing works
“146 147 – 149 ETBF toxin increases the expression of spermine oxidase (SMO) in HT29/c1 and T84 colonic epithelial cells, triggering the SMO-dependent production of ROS and activation of γ -H2A, which causes DNA damage.”
BackgroundThe Role of Cancer Stem Cells in Radiation Resistance
Arnold, C. R., Mangesius, J., Skvortsova, I., & Ganswindt, U. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.00164 · Cited by 214 · see citing works
Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy
Huang, R., Chen, H., Liang, J., Li, Y., Yang, J., Luo, C., Tang, Y., Ding, Y., Liu, X., Yuan, Q., et al. (2021) · Journal of Cancer · doi:10.7150/jca.54699 · Cited by 218 · see citing works
“Under oxidative stress, ROS regulate the activation of ATM, which recognizes DNA damage [138].”
BackgroundChaudhary, M. R., Chaudhary, S., Sharma, Y., Singh, T. A., Mishra, A. K., Sharma, S. G., & Mehdi, M. M. (2023) · Biogerontology · doi:10.1007/s10522-023-10050-1 · Cited by 210 · see citing works
Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview
Brillo, V., Chieregato, L., Leanza, L., Muccioli, S., & Costa, R. (2021) · Life · doi:10.3390/life11040332 · Cited by 202 · see citing works
“Intracellular ROS increase promotes a series of signaling cascades, including the activation of MAPK and NF-κB pathways; moreover, DNA damage induced by ROS accumulation can promote p53 accumulation, activating the p53/Bax pathway and resulting in apoptosis [117].”
BackgroundInfluentialCopper Complexes as Anticancer Agents Targeting Topoisomerases I and II
Molinaro, C., Martoriati, A., Pélinski, L., & Cailliau, K. (2020) · Cancers · doi:10.3390/cancers12102863 · Cited by 200 · see citing works
Salivary gland function, development, and regeneration
Chibly, A. M., Aure, M. H., Patel, V. N., & Hoffman, M. P. (2022) · Physiological Reviews · doi:10.1152/physrev.00015.2021 · Cited by 207 · see citing works
Rauf, A., Khalil, A. A., Awadallah, S. M., Khan, S. A., Abu‐Izneid, T., Kamran, M., Hemeg, H. A., Mubarak, M. S., Khalid, A., & Wilairatana, P. (2023) · Food Science & Nutrition · doi:10.1002/fsn3.3784 · Cited by 201 · see citing works
Antioxidant Therapy in Cancer: Rationale and Progress
Luo, M., Zhou, L., Huang, Z., Li, B., Nice, E. C., Xu, J., & Huang, C. (2022) · Antioxidants · doi:10.3390/antiox11061128 · Cited by 201 · see citing works
Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases
Huang, P., Chen, G., Jin, W., Mao, K., Wan, H., & He, Y. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137292 · Cited by 193 · see citing works
Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy
Zhang, Q., Kuang, G., Li, W., Wang, J., Ren, H., & Zhao, Y. (2023) · Nano-Micro Letters · doi:10.1007/s40820-023-01018-4 · Cited by 190 · see citing works
Ma, S., Song, W., Xu, Y., Si, X., Lv, S., Zhang, Y., Tang, Z., & Chen, X. (2020) · Nano Letters · doi:10.1021/acs.nanolett.9b05265 · Cited by 180 · see citing works
Cytotoxic mechanisms of doxorubicin at clinically relevant concentrations in breast cancer cells
Nicoletto, R. E., & Ofner, C. M. (2022) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-022-04400-y · Cited by 178 · see citing works
“Detection of phosphorylated H2AX at Serine-139 allows for the quantification of DNA DSBs.”
BackgroundInfluentialNickel Carcinogenesis Mechanism: DNA Damage
Guo, H., Liu, H., Wu, H., Cui, H., Fang, J. S., Zuo, Z., Deng, J., Li, Y., Wang, X., & Zhao, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194690 · Cited by 176 · see citing works
Shin, J., Song, M.-H., Oh, J.-W., Keum, Y.-S., & Saini, R. K. (2020) · Antioxidants · doi:10.3390/antiox9060532 · Cited by 173 · see citing works
“In the human body, a range of short-lived reactive oxygen species (ROS), including superoxide radical/anion (O2•−), hydroxyl radical (•OH), and hydrogen peroxide H2O2 are endogenously produced by mitochondria (electron transport chain), NADPH oxidase, peroxisomes, and endoplasmic reticulum (as byproducts during the ce…”
BackgroundThe gold complex auranofin: new perspectives for cancer therapy
Abdalbari, F. H., & Telleria, C. M. (2021) · Discover Oncology · doi:10.1007/s12672-021-00439-0 · Cited by 169 · see citing works
Shi, Y., Zhu, X.-T., Su-na, Z., Ma, Y., Han, Y., Yue, J., & Zhang, Y. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1172481 · Cited by 179 · see citing works
“transduction within DDR, interfering with cell cycle progression, and inducing p53 transcriptional response and apoptosis (32).”
BackgroundReactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease
Zhang, Z., Dalan, R., Hu, Z., Wang, J., Chew, N., Poh, K. K., Tan, R., Soong, T. W., Dai, Y., Ye, L., et al. (2022) · Advanced Materials · doi:10.1002/adma.202202169 · Cited by 174 · see citing works
Recent advances in MOF-based nanoplatforms generating reactive species for chemodynamic therapy
Zhong, Y., Li, X., Chen, J., Wang, X., Wei, L.-T., Fang, L., Kumar, A., Zhuang, S., & Liu, J. (2020) · Dalton Transactions · doi:10.1039/d0dt01882a · Cited by 158 · see citing works
Xue, T., Xu, C., Wang, Y., Wang, Y., Tian, H., & Zhang, Y. (2019) · Biomaterials Science · doi:10.1039/c9bm01044k · Cited by 157 · see citing works
Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy
Bai, S., Lan, Y., Fu, S., Cheng, H., Lu, Z., & Liu, G. (2022) · Nano-Micro Letters · doi:10.1007/s40820-022-00894-6 · Cited by 155 · see citing works
“Although free radicals are generally thought to exert antitumor effects through directly attack on the double stranded DNA structure and causing irreversible DNA damage, cytotoxic free radicalinduced dysregulation of associated calcium signaling is also thought to be the cause of cell apoptosis, which explains why the…”
BackgroundImpact of heavy metal toxicity on the human health and environment
Kotnala, S., Tiwari, S., Nayak, A., Bhushan, B., Chandra, S., Medeiros, C. R., & Coutinho, H. D. M. (2025) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2025.179785 · Cited by 162 · see citing works
Altered glucose metabolism and cell function in keloid fibroblasts under hypoxia
Wang, Q., Wang, P., Qin, Z., Yang, X. C., Pan, B., Nie, F., & Bi, H. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101815 · Cited by 153 · see citing works
“A growing body of data revealed that ROS level increased in cells exposed to hypoxia [30, 31], while other researchers detected the opposite result.”
ResultCircadian rhythms and cancers: the intrinsic links and therapeutic potentials
Zhou, L., Zhang, Z., Nice, E. C., Huang, C., Zhang, W., & Tang, Y. C. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01238-y · Cited by 156 · see citing works
Li, C., Deng, C., Wang, S., Dong, X. D., Dai, B., Guo, W., Guo, Q., Feng, Y., Xu, H., Song, X., et al. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103059 · Cited by 149 · see citing works
“While Cisplatin induces DNA single-strand breaks, activating the ATR-Chk1 pathway [24 – 26].”
BackgroundAntitumor Effects of Carvacrol and Thymol: A Systematic Review
Sampaio, L. A., Pina, L. T. S., Serafini, M. R., Tavares, D. D. S., & Guimarães, A. G. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.702487 · Cited by 148 · see citing works
Reactive oxygen species-powered cancer immunotherapy: Current status and challenges
He, M., Wang, M., Xu, T., Zhang, M., Dai, H., Wang, C., Ding, D., & Zhong, Z. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2023.02.040 · Cited by 144 · see citing works
Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer
Zeng, Z., Fu, M., Hu, Y., Wei, Y., Wei, X., & Luo, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01877-w · Cited by 143 · see citing works
“Moreover, studies have demonstrated how CSCs use ROS to resist radio-and chemotherapy-derived oxidative stress [324].”
BackgroundLi, J., Zhao, Y., Gong, S., Wang, M., Liu, X., He, Q., Li, Y., Huang, S., Qiao, H., Tan, X.-R., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36523-y · Cited by 143 · see citing works
Emerging carbon-supported single-atom catalysts for biomedical applications
Liao, G., Zhang, L., Li, C., Liu, S., Fang, B., & Yang, H. (2022) · Matter · doi:10.1016/j.matt.2022.07.031 · Cited by 134 · see citing works
Ren, Y., Wang, R., Weng, S., Xu, H., Zhang, Y., Chen, S., Liu, S., Ba, Y., Zhou, Z., Luo, P., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01831-w · Cited by 138 · see citing works
“On the other hand, ROS also oxidatively modify key signaling proteins and proteins involved in crucial biological mechanisms [4, 29, 30].”
BackgroundMechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy
Zheng, Z., Su, J., Bao, X., Wang, H., Bian, C., Zhao, Q., & Jiang, X. M. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1247268 · Cited by 135 · see citing works
“DNA is one of the main targets of ROS, which can induce DNA damage and induce DNA damage response (18).”
BackgroundSupramolecular hydrogels for wound repair and hemostasis
Zhuo, S., Liang, Y., Wu, Z., Zhao, X., Han, Y. N., & Guo, B. (2023) · Materials Horizons · doi:10.1039/d3mh01403g · Cited by 132 · see citing works
Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review
Olteanu, G., Neacșu, S. M., JOIȚA, F. A., Musuc, A. M., Lupu, C. E., Ioniță-Mîndrican, C.-B., Lupuliasa, D., & Mititelu, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073849 · Cited by 131 · see citing works
Qi, B., Song, L., Hu, L., Guo, D. S., Ren, G., Peng, T., Liu, M., Fang, Y., Li, C., Zhang, M., et al. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00800-5 · Cited by 126 · see citing works
Mechanisms and regulations of ferroptosis
Zhang, X.-D., Liu, Z., Wang, M.-S., Guo, Y.-X., Wang, X., Luo, K., Huang, S., & Li, R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1269451 · Cited by 131 · see citing works
Howard, D., Sebastian, S. T., Le, Q. V.-C., Thierry, B., & Kempson, I. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020579 · Cited by 125 · see citing works
“Out of these the double strand breaks causes are most important [29,34].”
BackgroundRole of Rad51 and DNA repair in cancer: A molecular perspective
Laurini, E., Marson, D., Fermeglia, A., Aulić, S., Fermeglia, M., & Pricl, S. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107492 · Cited by 128 · see citing works
The Importance of Being PI3K in the RAS Signaling Network
Cuesta, C., Arévalo-Alameda, C., & Castellano, E. (2021) · Genes · doi:10.3390/genes12071094 · Cited by 123 · see citing works
Gallic acid for cancer therapy: Molecular mechanisms and boosting efficacy by nanoscopical delivery
Ashrafizadeh, M., Zarrabi, A., Mirzaei, S., Hashemi, F., Samarghandian, S., Zabolian, A., Hushmandi, K., Ang, H. L., Sethi, G., Kumar, A. P., et al. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112576 · Cited by 124 · see citing works
Yi, G. Y., Kim, M. J., Kim, H. I., Park, J., & Baek, S. H. (2022) · Antioxidants · doi:10.3390/antiox11040625 · Cited by 121 · see citing works
ROS: A “booster” for chronic inflammation and tumor metastasis
Chen, A., Huang, H., Fang, S., & Hang, Q. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189175 · Cited by 127 · see citing works
Medicinal Prospects of Antioxidants From Algal Sources in Cancer Therapy
Ferdous, U. T., & Yusof, Z. N. B. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.593116 · Cited by 121 · see citing works
“Above all, these alterations of chromosomes give rise to genetic instability and ultimately lead to carcinogenesis (De Sá Junior et al., 2017; Srinivas et al., 2019).”
BackgroundOxidative Stress in Cancer Therapy: Friend or Enemy?
Azmanova, M., & Pitto‐Barry, A. (2022) · ChemBioChem · doi:10.1002/cbic.202100641 · Cited by 119 · see citing works
Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix?
Berdiaki, A., Neagu, M. T., Spyridaki, I., Николаевич, К. А., Pérez, S., & Nikitovic, D. (2023) · Antioxidants · doi:10.3390/antiox12040824 · Cited by 118 · see citing works
Ashrafizadeh, M., Bakhoda, M. R., Bahmanpour, Z., Ilkhani, K., Zarrabi, A., Makvandi, P., Khan, H. Z., Mazaheri, S., Darvish, M., & Mirzaei, H. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.00829 · Cited by 114 · see citing works
Recent Overview of Potent Antioxidant Activity of Coordination Compounds
El‐Lateef, H. M. A., El‐Dabea, T., Khalaf, M. M., & Abu‐Dief, A. M. (2023) · Antioxidants · doi:10.3390/antiox12020213 · Cited by 114 · see citing works
Sun, X., Wang, S., Gai, J., Guan, J., Li, J., Li, Y., Zhao, J., Zhao, C., Fu, L., & Li, Q. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00754 · Cited by 110 · see citing works
Zhou, T., Yang, X., Chen, Z., Yang, Y., Wang, X., Cao, X., Chen, C., Chen, H., Tian, H., Qin, A., et al. (2022) · Advanced Science · doi:10.1002/advs.202105466 · Cited by 108 · see citing works
Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies
Zhou, X., An, B., Lin, Y., Ni, Y., Zhao, X., & Liang, X. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115036 · Cited by 107 · see citing works
Regulation of seed germination: ROS, epigenetic, and hormonal aspects
Wang, Y., Sun, X., Peng, J., Li, F., Ali, F., & Wang, Z. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.06.001 · Cited by 108 · see citing works
“The formation of hydroxyl radicals at a higher level in the mitochondria of seeds results in a higher degree of damage to mitochondrial DNA and activation of the antioxidant defense system [70,71].”
Zhang, C., Xin, L., Li, J., Cao, J., Sun, Y., Wang, X., Luo, J., Zeng, Y., Li, Q., Zhang, Y., et al. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202101946 · Cited by 106 · see citing works
Krawczyk, M., Burzyńska-Pędziwiatr, I., Woźniak, L. A., & Bukowiecka‐Matusiak, M. (2023) · Biomolecules · doi:10.3390/biom13091402 · Cited by 114 · see citing works
“This can lead to mutations, carcinogenesis, apoptosis, necrosis, and hereditary diseases [43].”
BackgroundCancer cell membrane-coated nanoparticles: a promising anti-tumor bionic platform
Guo, Q., Wang, S., Xu, R., Tang, Y., & Xia, X. (2024) · RSC Advances · doi:10.1039/d4ra01026d · Cited by 108 · see citing works
“145 In recent years other metal ion ( e.g. , Cu 2+ and Mn 2+ ) mediated Fenton-like reactions have also been developed for CTD enhancement.”
BackgroundLow‐Density Neutrophils in Systemic Lupus Erythematosus
Tay, S. H., Celhar, T., & Fairhurst, A. (2020) · Arthritis & Rheumatology · doi:10.1002/art.41395 · Cited by 107 · see citing works
“Consistent with these findings, chronically elevated ROS, which often occurs in SLE, affects several aspects of DNA damage response and may lead to accumulation of such genomic changes (57,58).”
BackgroundRole of Mitochondria in Cancer Stem Cell Resistance
García-Heredia, J. M., & Carnero, A. (2020) · Cells · doi:10.3390/cells9071693 · Cited by 85 · see citing works
Emerging roles of cystathionine β-synthase in various forms of cancer
Ascenção, K., & Szabó, C. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102331 · Cited by 105 · see citing works
Sirtuins' control of autophagy and mitophagy in cancer
Aventaggiato, M., Vernucci, E., Barreca, F., Russo, M. A., & Tafani, M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107748 · Cited by 103 · see citing works
Ammonia detoxification promotes CD8+ T cell memory development by urea and citrulline cycles
Tang, K., Zhang, H., Deng, J., Wang, D., Liu, S., Lu, S., Cui, Q., Chen, C., Liu, J., Yang, Z., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01365-1 · Cited by 104 · see citing works
Myeloperoxidase: Growing importance in cancer pathogenesis and potential drug target
Valadez-Cosmes, P., Raftopoulou, S., Mihalič, Z. N., Marsche, G., & Kargl, J. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.108052 · Cited by 104 · see citing works
Mechano-signaling via Piezo1 prevents activation and p53-mediated senescence of muscle stem cells
Peng, Y., Du, J., Günther, S., Guo, X., Wang, S., Schneider, A., Zhu, L., & Braun, T. W. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102309 · Cited by 106 · see citing works
“Increased production of ROS promotes accumulation of P53 in numerous cell types [37,38], which sparked the idea that the enhanced presence of P53 in Piezo1scKO MuSCs is due to increased ROS production.”
BackgroundTargeting innate sensing in the tumor microenvironment to improve immunotherapy
Liu, Z., Han, C., & Fu, Y. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0341-y · Cited by 102 · see citing works
“Radiation directly kills cancer cells by inducing DNA damage and increasing reactive oxygen species (ROS) levels, which will restrict the proliferation of irradiated cells and promote cell apoptosis.(125) Intriguingly, our previous study first revealed that the adaptive immune system was required for the optimal antit…”
BackgroundFerrari, E., Bettuzzi, S., & Naponelli, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116075 · Cited by 102 · see citing works
ROS and TGFβ: from pancreatic tumour growth to metastasis
Chang, C., & Pauklin, S. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01960-4 · Cited by 100 · see citing works
“Elevated ROS has foremostly an anti-proliferative effect in benign pancreatic tissue by activating the DNA damage response pathways that block cell proliferation or lead to apoptosis upon too extensive cellular damage [27].”
BackgroundMa, H.-J., Kang, Z.-H., Foo, T., Shen, Z.-Y., & Xia, B. (2022) · Hepatology · doi:10.1002/hep.32335 · Cited by 82 · see citing works
“[9,10] Oxidative stress results from an imbalance between reactive oxygen species (ROS) production and removal.[11] As a major endogenous cause of DNA damage, this imbalance can cause oxidized lesions in DNA, which are highly damaging and carry a high mutagenic potency.”
BackgroundZhou, S., Cai, H., He, X., Tang, Z., & Lu, S. (2023) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2023.215536 · Cited by 101 · see citing works
Vaneev, A. N., Gorelkin, P. V., Garanina, A. S., Lopatukhina, H., Vodopyanov, S., Alova, A. V., Ryabaya, O. O., Akasov, R., Zhang, Y., Novák, P., et al. (2020) · Analytical Chemistry · doi:10.1021/acs.analchem.0c01256 · Cited by 101 · see citing works
Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications
Akter, S., Madhuvilakku, R., Kar, A. K., Nila, I. S., Liu, P., Inuzuka, H., Wei, W., & Hong, Y. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02583-x · Cited by 119 · see citing works
The micro(nano)plastics perspective: exploring cancer development and therapy
Deng, X., Gui, Y., & Zhao, L. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02230-z · Cited by 99 · see citing works
“Oxidative stress refers to the accumulation of reactive oxygen species (ROS) in the body, which are capable of triggering DNA damage [35], leading to genetic mutations and thus increasing the risk of cancer.”
Density functional theory studies of the antioxidants—a review
Mahmoudi, S., Dehkordi, M. M., & Asgarshamsi, M. H. (2021) · Journal of Molecular Modeling · doi:10.1007/s00894-021-04891-1 · Cited by 97 · see citing works
Molecular Mechanism of β-Sitosterol and its Derivatives in Tumor Progression
Bao, X., Zhang, Y., Zhang, H., & Xia, L. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.926975 · Cited by 97 · see citing works
The Biochemistry and Effectiveness of Antioxidants in Food, Fruits, and Marine Algae
Pruteanu, L.-L., Bailey, D. S., Grădinaru, A. C., & Jäntschi, L. (2023) · Antioxidants · doi:10.3390/antiox12040860 · Cited by 114 · see citing works
Exploring the Application of Micellar Drug Delivery Systems in Cancer Nanomedicine
Wang, Q., Atluri, K., Tiwari, A. K., & Babu, R. J. (2023) · Pharmaceuticals · doi:10.3390/ph16030433 · Cited by 100 · see citing works
“The production of ROS, particularly hydrogen peroxide (H2O2), is essential for several physiological activities [23,24].”
BackgroundRadiotherapy modulates tumor cell fate decisions: a review
Chen, H., Han, Z., Luo, Q., Wang, Y., Li, Q., Zhou, L., & Zuo, H.-D. (2022) · Radiation Oncology · doi:10.1186/s13014-022-02171-7 · Cited by 95 · see citing works
Wang, M., Kim, R., Kohonen‐Corish, M. R. J., Chen, H., Donovan, C., & Oliver, B. G. G. (2025) · British Journal of Cancer · doi:10.1038/s41416-025-02999-2 · Cited by 96 · see citing works
“Oxidative damage also plays an important role in the development of many cancers [89, 90].”
Zhang, X., Yu, S., Li, X., Wen, X., Liu, S., Zu, R., Ren, H., Li, T. X., Yang, C., & Luo, H. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106777 · Cited by 94 · see citing works
- Authors
- Srinivas, U. S., Tan, B. W. Q., Vellayappan, B. A., & Jeyasekharan, A. D.
- Affiliations
- National University of Singapore (SG)
- National University Hospital (SG)
- Corresponding author
- Jeyasekharan, Anand D.
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 25
- Pages
- 101084
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC6859528
- OpenAlex
- W2906120852
- Cited by
- 2,144
- References
- 153
- Citations by year
- 2026: 217 · 2025: 396 · 2024: 392 · 2023: 381 · 2022: 335 · 2021: 262 · 2020: 132 · 2019: 26
- FWCI
- 10.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Medical Research Council (NMRC/TA/0052/2016)
- AstraZeneca
- Ministry of Health -Singapore
- Meso Scale Diagnostics
- National Research Foundation Singapore
- Ministry of Education - Singapore
- Janssen Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- reactive oxygen species, DNA damage response, cancer, DNA double-strand breaks, genotoxic stress, anticancer agents, ionizing radiation, radiosensitizers, combination therapy, oxidative DNA damage
- MeSH terms
- Animals, DNA Damage, DNA Repair, Humans, Neoplasms, Tumor Suppressor Protein p53, Apoptosis, Reactive Oxygen Species
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
