Progress towards a clinically-successful ATR inhibitor for cancer therapy

The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment,...

Full description

Saved in:
Bibliographic Details
Published inCurrent research in pharmacology and drug discovery Vol. 2; p. 100017
Main Authors Barnieh, Francis M., Loadman, Paul M., Falconer, Robert A.
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 01.01.2021
Elsevier
Subjects
ATM
ATR
ATR inhibitors
Chemo- and radiosensitisers
DDR
Review
Chemo- and radiosensitisers
ATM
DDR
ATR inhibitors
ATR
Online AccessGet full text

Cover

Abstract The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just as monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions. [Display omitted] •The DNA Damage Response (DDR) is of significant interest in cancer research.•ATR kinase is a promising target for cancer therapeutics and drug discovery.•ATR kinase inhibitors have recently begun evaluation in cancer clinical trials.•First comprehensive review of the history and current status of ATR inhibitor development.
AbstractList The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just as monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions.The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just as monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions.
The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just as monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions.
The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just as monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions. [Display omitted] •The DNA Damage Response (DDR) is of significant interest in cancer research.•ATR kinase is a promising target for cancer therapeutics and drug discovery.•ATR kinase inhibitors have recently begun evaluation in cancer clinical trials.•First comprehensive review of the history and current status of ATR inhibitor development.
The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has demonstrated significant therapeutic potential in cancer treatment, with ATR inhibitors having shown anti-tumour activity not just as monotherapies, but also in potentiating the effects of conventional chemotherapy, radiotherapy, and immunotherapy. This review focuses on the biology of ATR, its functional role in cancer development and treatment, and the rationale behind inhibition of this target as a therapeutic approach, including evaluation of the progress and current status of development of potent and specific ATR inhibitors that have emerged in recent decades. The current applications of these inhibitors both in preclinical and clinical studies either as single agents or in combinations with chemotherapy, radiotherapy and immunotherapy are also extensively discussed. This review concludes with some insights into the various concerns raised or observed with ATR inhibition in both the preclinical and clinical settings, with some suggested solutions. Image 1 • The DNA Damage Response (DDR) is of significant interest in cancer research. • ATR kinase is a promising target for cancer therapeutics and drug discovery. • ATR kinase inhibitors have recently begun evaluation in cancer clinical trials. • First comprehensive review of the history and current status of ATR inhibitor development.
ArticleNumber 100017
Author Falconer, Robert A.
Barnieh, Francis M.
Loadman, Paul M.
Author_xml – sequence: 1
  givenname: Francis M.
  surname: Barnieh
  fullname: Barnieh, Francis M.
– sequence: 2
  givenname: Paul M.
  orcidid: 0000-0002-4259-8616
  surname: Loadman
  fullname: Loadman, Paul M.
– sequence: 3
  givenname: Robert A.
  orcidid: 0000-0002-6426-4430
  surname: Falconer
  fullname: Falconer, Robert A.
  email: r.a.falconer1@bradford.ac.uk
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34909652$$D View this record in MEDLINE/PubMed
BookMark eNqFkUFv1DAQhSNUREvpP0AoRy5ZxokTxxyQqorCSpVAqJytycTe9cobL3bSav893mapWg5wsGzNvPfGmu91djL4QWfZWwYLBqz5sFlQ2K0xLEooWSoBMPEiOytrCUVZC3by5H2aXcS4SZJSSA5N-yo7rbgE2dTlWbb8Hvwq6Bjz0d9j6GOOOTk7WELn9kWciFLTTC6_vP2R22FtOzv6kJt0CAfSIR_XOuBu_yZ7adBFfXG8z7Of159vr74WN9--LK8ubwqqGYgCkRmsWyyhE9xAK6EHw1peM0QjiTqOxKkHLipTMW1I9g3n3HBhWlkbqM6z5Zzbe9yoXbBbDHvl0aqHgg8rhWG05LRiTFasRoFaCK7BdNAh8LKueqoNNTplfZqzdlO31T3pYQzonoU-7wx2rVb-TrVNU0lRpoD3x4Dgf006jmprI2nncNB-iqpsGHAQTdMm6bunsx6H_GGRBHwWUPAxBm0eJQzUgbraqJm6OlBXM_Vk-_iXjeyIo_WHH1v3P_NxAToRu7M6qEhWJ6y9DZrGtFL774DfWdnK4A
CitedBy_id crossref_primary_10_1016_j_procbio_2024_05_024
crossref_primary_10_1007_s00280_022_04436_0
crossref_primary_10_1021_acs_jmedchem_3c01917
crossref_primary_10_1002_advs_202403831
crossref_primary_10_1007_s00280_021_04388_x
crossref_primary_10_1016_j_ijrobp_2021_07_1708
crossref_primary_10_1016_j_bcp_2022_115095
crossref_primary_10_1186_s13046_022_02469_0
crossref_primary_10_1158_1078_0432_CCR_22_2861
crossref_primary_10_3389_fimmu_2023_1138920
crossref_primary_10_1016_j_mcpro_2024_100802
crossref_primary_10_1002_mco2_788
crossref_primary_10_1186_s12967_023_04634_1
crossref_primary_10_1186_s13045_024_01613_x
crossref_primary_10_1007_s42764_021_00049_8
crossref_primary_10_3390_ijms24054741
crossref_primary_10_1002_cjp2_350
crossref_primary_10_1016_j_cbi_2023_110740
crossref_primary_10_1038_s41392_023_01548_8
crossref_primary_10_1002_mc_23384
crossref_primary_10_1097_HEP_0000000000000420
crossref_primary_10_3389_fonc_2022_981332
crossref_primary_10_3390_cancers15020448
crossref_primary_10_1158_0008_5472_CAN_21_2997
crossref_primary_10_1016_j_ejphar_2024_176647
crossref_primary_10_1038_s41375_024_02138_5
crossref_primary_10_1158_1078_0432_CCR_22_1184
crossref_primary_10_3390_ijms232314672
crossref_primary_10_3390_ijms242316637
crossref_primary_10_2139_ssrn_3869893
crossref_primary_10_3390_ijms241210212
crossref_primary_10_1136_jitc_2023_007560
crossref_primary_10_1016_j_bcp_2024_116254
crossref_primary_10_3389_fcvm_2022_878268
crossref_primary_10_3389_fonc_2021_778925
crossref_primary_10_3390_cancers16203536
crossref_primary_10_1016_j_celrep_2023_112495
crossref_primary_10_1016_j_dnarep_2022_103384
crossref_primary_10_1021_acs_jmedchem_3c02476
crossref_primary_10_1016_j_jconrel_2022_03_049
crossref_primary_10_1016_j_isci_2023_106372
crossref_primary_10_1126_scisignal_adl6445
crossref_primary_10_1038_s41418_023_01196_z
crossref_primary_10_3390_cancers14164050
crossref_primary_10_2174_0115680096280750240123054936
crossref_primary_10_1002_mc_23716
crossref_primary_10_1038_s41568_022_00490_1
crossref_primary_10_3390_cancers16010083
crossref_primary_10_1002_1878_0261_13224
crossref_primary_10_1186_s13014_022_02052_z
crossref_primary_10_1042_BST20220729
crossref_primary_10_3390_ph15121475
crossref_primary_10_1016_j_tranon_2025_102359
crossref_primary_10_1172_jci_insight_156087
crossref_primary_10_1016_j_ygyno_2024_10_009
crossref_primary_10_1016_j_bbadis_2024_167448
crossref_primary_10_3390_cancers17030359
crossref_primary_10_3390_pharmaceutics15122761
crossref_primary_10_1016_j_molcel_2022_12_031
crossref_primary_10_1158_1078_0432_CCR_22_0875
crossref_primary_10_3390_cancers13236008
crossref_primary_10_3390_cancers14071821
crossref_primary_10_3390_biomedicines10112775
crossref_primary_10_3390_cells11091466
crossref_primary_10_1021_acs_jmedchem_4c01595
crossref_primary_10_1158_1535_7163_MCT_23_0402
crossref_primary_10_3390_cells11091463
crossref_primary_10_1038_s41571_024_00863_5
crossref_primary_10_1080_13543776_2022_2027911
crossref_primary_10_1097_PPO_0000000000000561
crossref_primary_10_1016_j_semcancer_2024_02_002
crossref_primary_10_3389_fonc_2022_998388
crossref_primary_10_3389_fcell_2023_1200466
crossref_primary_10_1186_s13062_021_00313_7
crossref_primary_10_1002_cncr_34683
Cites_doi 10.1200/JCO.2016.34.15_suppl.2513
10.1016/S0065-230X(01)83007-4
10.1111/cas.13947
10.1158/0008-5472.CAN-09-0823
10.1016/j.pharmthera.2020.107518
10.1038/sj.onc.1204252
10.1016/S0968-0004(00)01563-2
10.1101/gad.914401
10.1038/nature03482
10.1016/j.cell.2011.03.044
10.1158/1538-7445.AM2012-1823
10.3390/ph3051311
10.1016/j.neo.2018.03.003
10.1158/1078-0432.CCR-15-0479
10.1091/mbc.9.9.2361
10.1074/jbc.M410873200
10.1002/cncr.21536
10.1158/0008-5472.CAN-16-3398
10.1016/j.cell.2005.12.041
10.1021/ml500352s
10.1200/JCO.2019.37.15_suppl.3007
10.1038/ncb1145
10.18632/oncotarget.2158
10.1038/bjc.2011.243
10.1016/j.canlet.2006.03.009
10.1158/0008-5472.CAN-09-2715
10.1200/JCO.2017.76.6915
10.1158/1535-7163.MCT-19-0019
10.1101/gad.14.4.397
10.1158/1535-7163.MCT-16-0239
10.1158/0008-5472.CAN-10-2286
10.1634/theoncologist.2016-0145
10.1016/j.tibs.2010.09.005
10.1002/pbc.26825
10.1126/science.1140321
10.1038/nature03445
10.1021/acs.jmedchem.8b01187
10.1021/mp400760b
10.1128/MCB.22.6.1834-1843.2002
10.1038/sj.bjc.6603535
10.1038/cddis.2012.181
10.1038/nsmb.2189
10.1002/ijc.30373
10.1158/1538-7445.AM2017-983
10.1158/2159-8290.CD-16-0860
10.1101/gad.1897010
10.1158/0008-5472.CAN-13-3369
10.1371/journal.pone.0119214
10.1093/annonc/mdv084.3
10.3390/cancers10080275
10.1016/j.cell.2011.02.013
10.1016/S0140-6736(15)60373-7
10.1016/S0092-8674(00)81479-8
10.1158/1535-7163.763.3.7
10.1093/nar/gkp593
10.1126/science.281.5383.1677
10.3109/10715762.2011.638291
10.1016/j.bcp.2019.04.022
10.1158/1538-7445.AM2016-CT012
10.1038/nrc1691
10.1093/mutage/geh025
10.1158/0008-5472.CAN-13-0110
10.1038/nature05268
10.1038/emboj.2009.281
10.1016/S0955-0674(00)00280-5
10.1172/JCI122622
10.1158/0008-5472.CAN-18-2807
10.1016/S1535-6108(03)00048-5
10.1126/science.277.5331.1497
10.4155/fmc.15.33
10.1074/jbc.M513265200
10.1016/j.biomaterials.2018.06.024
10.1016/j.ijrobp.2005.09.031
10.1158/1535-7163.MCT-18-0010
10.1158/1535-7163.MCT-16-0378
10.1093/annonc/mdy292.059
10.1021/jm101520v
10.1021/acs.jmedchem.9b00426
10.1158/1538-7445.AM2013-3343
10.1016/j.ctrv.2015.11.008
10.1016/S0092-8674(00)81683-9
10.1126/science.1065521
10.1021/jm301859s
10.1158/1535-7163.TARG-15-PR14
10.1158/1538-7445.AM2019-369
10.1016/S1535-6108(03)00110-7
10.1074/jbc.M300229200
10.1158/1078-0432.CCR-18-1821
10.1016/j.canlet.2016.09.024
10.1021/jm101488z
10.1038/nsmb.2076
10.1038/nature01368
10.1146/annurev.biochem.73.011303.073723
10.1016/j.molonc.2015.09.009
10.1038/nrm2450
10.1016/j.oraloncology.2005.06.003
10.1016/j.bmcl.2012.04.036
10.4161/cbt.21093
10.1038/35056049
10.1158/1538-7445.AM2013-2348
10.1038/nrm2858
10.1038/nchembio.573
10.1172/JCI96519
10.1038/nature03485
10.1158/1535-7163.MCT-08-0017
10.1038/ng1129
10.1158/1535-7163.MCT-18-0972
10.1016/j.ctrv.2017.08.013
10.1016/j.radonc.2016.10.023
10.1358/dot.2016.52.1.2440714
10.18632/oncotarget.6247
10.1016/j.canlet.2018.06.010
10.1016/j.pharmthera.2014.12.001
10.1158/1538-7445.AM2018-CT026
10.3390/cancers9050041
10.1056/NEJMoa0900212
10.1038/nature05236
10.1016/j.tma.2020.01.002
10.1007/s11523-017-0482-9
10.2217/fon.15.257
10.1128/MCB.00326-08
10.1124/mol.105.012716
10.1200/JCO.2016.34.15_suppl.2504
10.1016/j.stem.2018.09.016
10.1093/hmg/ddh335
10.1038/cr.2014.147
10.1158/1538-7445.AM2019-350
10.1073/pnas.161281798
10.1172/JCI58928
10.1038/nature08467
10.1016/j.tips.2011.02.014
10.1038/bjc.2012.265
10.1007/s10549-018-4683-4
10.1021/jm990628o
10.1016/0092-8674(92)90593-2
10.1186/s13578-020-0376-x
10.1073/pnas.1120508109
10.1371/journal.pone.0028335
10.1038/nature12634
10.1016/j.stem.2007.03.002
10.1074/jbc.M412065200
10.1016/S0959-8049(16)32607-7
10.1038/nature03443
10.1038/onc.2011.358
10.1016/j.ygyno.2017.10.003
10.1101/gad.452308
10.1158/0008-5472.CAN-12-1702
10.1021/ml500353p
10.1158/1535-7163.MCT-18-0470
10.4161/cbt.23761
10.1016/j.molmed.2006.07.007
10.1101/gad.1067403
10.1101/gad.1815309
ContentType Journal Article
Copyright 2021
Crown Copyright © 2021 Published by Elsevier B.V.
Crown Copyright © 2021 Published by Elsevier B.V. 2021
Copyright_xml – notice: 2021
– notice: Crown Copyright © 2021 Published by Elsevier B.V.
– notice: Crown Copyright © 2021 Published by Elsevier B.V. 2021
DBID 6I.
AAFTH
AAYXX
CITATION
NPM
7X8
5PM
DOA
DOI 10.1016/j.crphar.2021.100017
DatabaseName ScienceDirect Open Access Titles
Elsevier:ScienceDirect:Open Access
CrossRef
PubMed
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
PubMed
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic

PubMed
Database_xml – sequence: 1
  dbid: DOA
  name: Acceso a contenido Full Text - Doaj
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Pharmacy, Therapeutics, & Pharmacology
EISSN 2590-2571
ExternalDocumentID oai_doaj_org_article_119315a7ae774e0fb0ba04253dc5fc6e
PMC8663972
34909652
10_1016_j_crphar_2021_100017
S2590257121000043
Genre Journal Article
Review
GroupedDBID 6I.
AAEDW
AAFTH
AAXUO
ALMA_UNASSIGNED_HOLDINGS
AMRAJ
EBS
FDB
GROUPED_DOAJ
M41
M~E
OK1
ROL
RPM
0R~
AALRI
AAYWO
AAYXX
ACVFH
ADCNI
ADVLN
AEUPX
AFJKZ
AFPUW
AIGII
AITUG
AKBMS
AKYEP
APXCP
CITATION
0SF
NPM
7X8
5PM
ID FETCH-LOGICAL-c5107-aa1fa58a20b74f0890d0f18451aaf9ccb4ac4cd0473f31efc9d6444f47f895f03
IEDL.DBID DOA
ISSN 2590-2571
IngestDate Wed Aug 27 01:15:51 EDT 2025
Thu Aug 21 18:32:06 EDT 2025
Fri Jul 11 08:56:31 EDT 2025
Thu Jan 02 22:45:23 EST 2025
Tue Jul 01 02:38:07 EDT 2025
Thu Apr 24 23:12:31 EDT 2025
Tue Jul 25 20:58:54 EDT 2023
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Keywords Chemo- and radiosensitisers
ATM
DDR
ATR inhibitors
ATR
Language English
License This is an open access article under the CC BY-NC-ND license.
Crown Copyright © 2021 Published by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c5107-aa1fa58a20b74f0890d0f18451aaf9ccb4ac4cd0473f31efc9d6444f47f895f03
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ORCID 0000-0002-4259-8616
0000-0002-6426-4430
OpenAccessLink https://doaj.org/article/119315a7ae774e0fb0ba04253dc5fc6e
PMID 34909652
PQID 2610407668
PQPubID 23479
ParticipantIDs doaj_primary_oai_doaj_org_article_119315a7ae774e0fb0ba04253dc5fc6e
pubmedcentral_primary_oai_pubmedcentral_nih_gov_8663972
proquest_miscellaneous_2610407668
pubmed_primary_34909652
crossref_primary_10_1016_j_crphar_2021_100017
crossref_citationtrail_10_1016_j_crphar_2021_100017
elsevier_sciencedirect_doi_10_1016_j_crphar_2021_100017
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2021-01-01
PublicationDateYYYYMMDD 2021-01-01
PublicationDate_xml – month: 01
  year: 2021
  text: 2021-01-01
  day: 01
PublicationDecade 2020
PublicationPlace Netherlands
PublicationPlace_xml – name: Netherlands
PublicationTitle Current research in pharmacology and drug discovery
PublicationTitleAlternate Curr Res Pharmacol Drug Discov
PublicationYear 2021
Publisher Elsevier B.V
Elsevier
Publisher_xml – name: Elsevier B.V
– name: Elsevier
References Al-Subhi (bib2) 2018; 169
Taylor, Stark (bib140) 2001; 20
Bitler, Watson, Wheeler, Behbakht (bib16) 2017; 147
Murga (bib102) 2011; 18
Vendetti (bib148) 2015; 6
Jiang (bib66) 2009; 23
Barnieh, Race, Shnyder, Loadman, Falconer (bib8) 2019; 79
Plummer (bib117) 2018; 29
Barsanti (bib9) 2015; 6
Hanahan, Weinberg (bib60) 2011; 144
Yap (bib162) 2016; 69
Helt, Cliby, Keng, Bambara, O'Reilly (bib61) 2005; 280
Shechter, Costanzo, Gautier (bib133) 2004; 6
Fazio (bib39) 2016; 36
Kaelin (bib73) 2005; 5
Foote (bib46) 2013; 56
Thomas (bib142) 2017; 36
Combes (bib32) 2019; 79
Chen (bib29) 2018; 178
Schmitt (bib129) 2017; 77
Kandoth (bib74) 2013; 502
Liu, Zhang, Liu, Ding, Hu (bib91) 2012; 7
Nagel (bib104) 2019; 18
Bao (bib7) 2006; 444
Vendetti (bib149) 2018; 128
Bosotti, Isacchi, Sonnhammer (bib19) 2000; 25
Xu (bib159) 2011; 6
Foote (bib48) 2018; 61
Kastan (bib78) 1992; 71
Nishida (bib108) 2009; 37
Wengner (bib154) 2020; 19
Jin (bib68) 2018; 20
Arris (bib5) 2000; 43
Abraham (bib1) 2001; 15
Farmer (bib38) 2005; 434
Matsuoka (bib97) 2007; 316
Sun, Xu, Lu, Pan, Hu, Schisandrin (bib138) 2007; 246
Ihle (bib63) 2004; 3
Wang (bib152) 2019; 110
Alderton (bib3) 2004; 13
Knegtel (bib80) 2019; 62
National Cancer Institute Website (bib105)
Sun (bib139) 2018; 8
Bartkova (bib13) 2005; 434
Fokas (bib44) 2012; 3
Garrett, Collins (bib49) 2011; 32
Thomas (bib143) 2018; 36
Min (bib101) 2017; 16
Negrini, Gorgoulis, Halazonetis (bib106) 2010; 11
Carrassa, Damia (bib27) 2017; 60
Ferrao, Bukczynska, Johnstone, McArthur (bib41) 2012; 31
Gorecki, Andrs, Rezacova, Korabecny (bib54) 2020; 210
Wieringa, van der Zee, de Vries, van Vugt (bib155) 2016; 42
Clack, Lau, Pierce, Smith, Stephens (bib31) 2015; 26
Dillon (bib36) 2017; 16
Xiao (bib158) 2003; 278
Liu (bib92) 2013; 73
Cimprich, Cortez (bib30) 2008; 9
Levy-Lahad, Friedman (bib89) 2007; 96
Bakkenist, Kastan (bib6) 2003; 421
Sancar, Lindsey-Boltz, Unsal-Kacmaz, Linn (bib125) 2004; 73
Zenke (bib163) 2019; 79
resTORbio (bib121) 2019
Lempiainen, Halazonetis (bib87) 2009; 28
Jiang, Li, Li, Bai, Zhang (bib67) 2019; 11
Hall (bib57) 2014; 5
Leszczynska (bib88) 2016; 121
Thandavarayan (bib141) 2015; 10
Cortez, Guntuku, Qin, Elledge (bib33) 2001; 294
O'Carrigan (bib109) 2016; 34
Prevo (bib118) 2012; 13
Bukhari (bib24) 2019; 129
Charrier (bib28) 2011; 54
Alsubhi (bib4) 2016; 10
Gill (bib52) 2014; 11
Sarkaria (bib128) 1999; 59
Sorensen (bib136) 2003; 3
Krebs (bib82) 2018; 78
Carlo (bib26) 2016; 21
Qi (bib119) 2019; 164
Dillon (bib37) 2019; 25
Giridharan (bib53) 2012; 46
Konstantinidou (bib81) 2009; 69
Woods, Turchi (bib157) 2013; 14
Canman (bib25) 1998; 281
Seidel, Anderson, Blackburn (bib131) 2008; 28
Hammond, Denko, Dorie, Abraham, Giaccia (bib58) 2002; 22
Oliver (bib111) 2010; 24
Wise-Draper (bib156) 2017; 12
Tu (bib146) 2018; 17
De Bont, van Larebeke (bib35) 2004; 19
Karnitz (bib76) 2005; 68
Jossé (bib71) 2014; 74
Shapiro (bib132) 2016; 76
Luecking (bib93) 2017; 77
Ruzankina (bib124) 2007; 1
Yan (bib160) 2018; 23
Huntoon (bib62) 2013; 73
Kaeberlein (bib72) 2020; 4
Nghiem, Park, Kim, Vaziri, Schreiber (bib107) 2001; 98
Peasland (bib113) 2011; 105
De Bono (bib34) 2019; 37
Gilad (bib51) 2010; 70
Karve (bib77) 2012; 109
Shiloh, Kastan (bib135) 2001; 83
Sanchez (bib126) 1997; 277
Bartek, Lukas (bib12) 2003; 3
Bolt (bib17) 2005; 41
Bester (bib15) 2011; 145
Rundle, Bradbury, Drew, Curtin (bib123) 2017; 9
Wagner, Kaufmann (bib150) 2010; 3
Sarkaria (bib127) 1998; 58
Finlay (bib42) 2012; 22
Karnitz, Zou (bib75) 2015; 21
Brown, Baltimore (bib20) 2000; 14
Flynn, Zou (bib43) 2011; 36
Kim (bib79) 2017; 140
Jones, Blades, Foote, Guichard (bib70) 2013; 73
Plummer (bib116) 2016; 34
Bartkova (bib14) 2006; 444
Kwok (bib85) 2015; 385
Pires (bib114) 2010; 70
Roos, Kaina (bib122) 2006; 12
Weber, Ryan (bib153) 2015; 149
Bartek, Lukas (bib11) 2001; 13
Massey (bib96) 2016; 383
Brown, Baltimore (bib21) 2003; 17
Middleton, Pollard, Curtin (bib100) 2018; 10
van Gent, Hoeijmakers, Kanaar (bib147) 2001; 2
Foote, Lau, Nissink (bib47) 2015; 7
Myers, Cortez (bib103) 2006; 281
Schoppy (bib130) 2012; 122
Gorgoulis (bib55) 2005; 434
O'Driscoll, Ruiz-Perez, Woods, Jegg, Goodship (bib110) 2003; 33
Pires (bib115) 2012; 107
Bryant (bib23) 2005; 434
Johnson, Westcott (bib69) 2016; 12
Kurmasheva (bib84) 2018; 65
Toledo (bib145) 2011; 18
Sprong, Janssen, Vens, Begg (bib137) 2006; 64
Jacq (bib65) 2012; 72
McMahon, Van Buskirk, Dugan, Copeland, Cole (bib98) 1998; 94
Bornstein, Jimeno (bib18) 2016; 52
Jackson, Bartek (bib64) 2009; 461
Fernandes (bib40) 2005; 280
Guichard (bib56) 2013; 73
Marechal, Zou (bib95) 2015; 25
Fong (bib45) 2009; 361
Reaper (bib120) 2011; 7
Brown, O'Carrigan, Jackson, Yap (bib22) 2017; 7
Toledo, Murga, Gutierrez-Martinez, Soria, Fernandez-Capetillo (bib144) 2008; 22
Barsanti (bib10) 2015; 6
Menolfi, Zha (bib99) 2020; 10
Lavin (bib86) 2008; 9
Maira (bib94) 2008; 7
Hanahan, Weinberg (bib59) 2000; 100
Shi (bib134) 2018; 432
Yap (bib161) 2015; 14
Liu (bib90) 2011; 54
Wallez (bib151) 2018; 17
Pal (bib112) 2005; 104
Kumagai, Lee, Yoo, Dunphy (bib83) 2006; 124
Gately, Hittle, Chan, Yen (bib50) 1998; 9
Wise-Draper (10.1016/j.crphar.2021.100017_bib156) 2017; 12
Hammond (10.1016/j.crphar.2021.100017_bib58) 2002; 22
Yap (10.1016/j.crphar.2021.100017_bib162) 2016; 69
Min (10.1016/j.crphar.2021.100017_bib101) 2017; 16
Bakkenist (10.1016/j.crphar.2021.100017_bib6) 2003; 421
Bornstein (10.1016/j.crphar.2021.100017_bib18) 2016; 52
Clack (10.1016/j.crphar.2021.100017_bib31) 2015; 26
De Bono (10.1016/j.crphar.2021.100017_bib34) 2019; 37
Pal (10.1016/j.crphar.2021.100017_bib112) 2005; 104
Bitler (10.1016/j.crphar.2021.100017_bib16) 2017; 147
Taylor (10.1016/j.crphar.2021.100017_bib140) 2001; 20
Ferrao (10.1016/j.crphar.2021.100017_bib41) 2012; 31
Seidel (10.1016/j.crphar.2021.100017_bib131) 2008; 28
Bao (10.1016/j.crphar.2021.100017_bib7) 2006; 444
Barsanti (10.1016/j.crphar.2021.100017_bib10) 2015; 6
Dillon (10.1016/j.crphar.2021.100017_bib37) 2019; 25
Hanahan (10.1016/j.crphar.2021.100017_bib59) 2000; 100
Plummer (10.1016/j.crphar.2021.100017_bib116) 2016; 34
Shapiro (10.1016/j.crphar.2021.100017_bib132) 2016; 76
Gately (10.1016/j.crphar.2021.100017_bib50) 1998; 9
Wagner (10.1016/j.crphar.2021.100017_bib150) 2010; 3
Wang (10.1016/j.crphar.2021.100017_bib152) 2019; 110
Menolfi (10.1016/j.crphar.2021.100017_bib99) 2020; 10
Qi (10.1016/j.crphar.2021.100017_bib119) 2019; 164
Karnitz (10.1016/j.crphar.2021.100017_bib75) 2015; 21
Brown (10.1016/j.crphar.2021.100017_bib20) 2000; 14
Wieringa (10.1016/j.crphar.2021.100017_bib155) 2016; 42
Bolt (10.1016/j.crphar.2021.100017_bib17) 2005; 41
Yap (10.1016/j.crphar.2021.100017_bib161) 2015; 14
Konstantinidou (10.1016/j.crphar.2021.100017_bib81) 2009; 69
Garrett (10.1016/j.crphar.2021.100017_bib49) 2011; 32
Luecking (10.1016/j.crphar.2021.100017_bib93) 2017; 77
Dillon (10.1016/j.crphar.2021.100017_bib36) 2017; 16
Sun (10.1016/j.crphar.2021.100017_bib139) 2018; 8
Jiang (10.1016/j.crphar.2021.100017_bib66) 2009; 23
Rundle (10.1016/j.crphar.2021.100017_bib123) 2017; 9
Knegtel (10.1016/j.crphar.2021.100017_bib80) 2019; 62
Schmitt (10.1016/j.crphar.2021.100017_bib129) 2017; 77
Hall (10.1016/j.crphar.2021.100017_bib57) 2014; 5
Negrini (10.1016/j.crphar.2021.100017_bib106) 2010; 11
Fazio (10.1016/j.crphar.2021.100017_bib39) 2016; 36
Zenke (10.1016/j.crphar.2021.100017_bib163) 2019; 79
Ihle (10.1016/j.crphar.2021.100017_bib63) 2004; 3
Weber (10.1016/j.crphar.2021.100017_bib153) 2015; 149
Bester (10.1016/j.crphar.2021.100017_bib15) 2011; 145
Toledo (10.1016/j.crphar.2021.100017_bib144) 2008; 22
Jones (10.1016/j.crphar.2021.100017_bib70) 2013; 73
Foote (10.1016/j.crphar.2021.100017_bib47) 2015; 7
Nghiem (10.1016/j.crphar.2021.100017_bib107) 2001; 98
Flynn (10.1016/j.crphar.2021.100017_bib43) 2011; 36
Liu (10.1016/j.crphar.2021.100017_bib91) 2012; 7
Middleton (10.1016/j.crphar.2021.100017_bib100) 2018; 10
Murga (10.1016/j.crphar.2021.100017_bib102) 2011; 18
Bartek (10.1016/j.crphar.2021.100017_bib12) 2003; 3
Lempiainen (10.1016/j.crphar.2021.100017_bib87) 2009; 28
Maira (10.1016/j.crphar.2021.100017_bib94) 2008; 7
Brown (10.1016/j.crphar.2021.100017_bib21) 2003; 17
Jin (10.1016/j.crphar.2021.100017_bib68) 2018; 20
Toledo (10.1016/j.crphar.2021.100017_bib145) 2011; 18
Fernandes (10.1016/j.crphar.2021.100017_bib40) 2005; 280
Sanchez (10.1016/j.crphar.2021.100017_bib126) 1997; 277
Leszczynska (10.1016/j.crphar.2021.100017_bib88) 2016; 121
Wengner (10.1016/j.crphar.2021.100017_bib154) 2020; 19
Johnson (10.1016/j.crphar.2021.100017_bib69) 2016; 12
Nishida (10.1016/j.crphar.2021.100017_bib108) 2009; 37
Vendetti (10.1016/j.crphar.2021.100017_bib149) 2018; 128
Brown (10.1016/j.crphar.2021.100017_bib22) 2017; 7
Bryant (10.1016/j.crphar.2021.100017_bib23) 2005; 434
Bukhari (10.1016/j.crphar.2021.100017_bib24) 2019; 129
van Gent (10.1016/j.crphar.2021.100017_bib147) 2001; 2
Combes (10.1016/j.crphar.2021.100017_bib32) 2019; 79
Krebs (10.1016/j.crphar.2021.100017_bib82) 2018; 78
Cimprich (10.1016/j.crphar.2021.100017_bib30) 2008; 9
Wallez (10.1016/j.crphar.2021.100017_bib151) 2018; 17
Alsubhi (10.1016/j.crphar.2021.100017_bib4) 2016; 10
Shechter (10.1016/j.crphar.2021.100017_bib133) 2004; 6
Tu (10.1016/j.crphar.2021.100017_bib146) 2018; 17
Cortez (10.1016/j.crphar.2021.100017_bib33) 2001; 294
Ruzankina (10.1016/j.crphar.2021.100017_bib124) 2007; 1
Vendetti (10.1016/j.crphar.2021.100017_bib148) 2015; 6
Levy-Lahad (10.1016/j.crphar.2021.100017_bib89) 2007; 96
Schoppy (10.1016/j.crphar.2021.100017_bib130) 2012; 122
Bartek (10.1016/j.crphar.2021.100017_bib11) 2001; 13
Thandavarayan (10.1016/j.crphar.2021.100017_bib141) 2015; 10
Yan (10.1016/j.crphar.2021.100017_bib160) 2018; 23
Barsanti (10.1016/j.crphar.2021.100017_bib9) 2015; 6
Massey (10.1016/j.crphar.2021.100017_bib96) 2016; 383
Giridharan (10.1016/j.crphar.2021.100017_bib53) 2012; 46
Carrassa (10.1016/j.crphar.2021.100017_bib27) 2017; 60
Karve (10.1016/j.crphar.2021.100017_bib77) 2012; 109
Al-Subhi (10.1016/j.crphar.2021.100017_bib2) 2018; 169
Bartkova (10.1016/j.crphar.2021.100017_bib14) 2006; 444
Kandoth (10.1016/j.crphar.2021.100017_bib74) 2013; 502
Thomas (10.1016/j.crphar.2021.100017_bib143) 2018; 36
Prevo (10.1016/j.crphar.2021.100017_bib118) 2012; 13
Matsuoka (10.1016/j.crphar.2021.100017_bib97) 2007; 316
Kurmasheva (10.1016/j.crphar.2021.100017_bib84) 2018; 65
Sorensen (10.1016/j.crphar.2021.100017_bib136) 2003; 3
Finlay (10.1016/j.crphar.2021.100017_bib42) 2012; 22
Kastan (10.1016/j.crphar.2021.100017_bib78) 1992; 71
Myers (10.1016/j.crphar.2021.100017_bib103) 2006; 281
Canman (10.1016/j.crphar.2021.100017_bib25) 1998; 281
Jacq (10.1016/j.crphar.2021.100017_bib65) 2012; 72
De Bont (10.1016/j.crphar.2021.100017_bib35) 2004; 19
Hanahan (10.1016/j.crphar.2021.100017_bib60) 2011; 144
Karnitz (10.1016/j.crphar.2021.100017_bib76) 2005; 68
Liu (10.1016/j.crphar.2021.100017_bib92) 2013; 73
Woods (10.1016/j.crphar.2021.100017_bib157) 2013; 14
Fong (10.1016/j.crphar.2021.100017_bib45) 2009; 361
Sarkaria (10.1016/j.crphar.2021.100017_bib128) 1999; 59
Xiao (10.1016/j.crphar.2021.100017_bib158) 2003; 278
Farmer (10.1016/j.crphar.2021.100017_bib38) 2005; 434
Foote (10.1016/j.crphar.2021.100017_bib48) 2018; 61
Guichard (10.1016/j.crphar.2021.100017_bib56) 2013; 73
Chen (10.1016/j.crphar.2021.100017_bib29) 2018; 178
Jackson (10.1016/j.crphar.2021.100017_bib64) 2009; 461
Reaper (10.1016/j.crphar.2021.100017_bib120) 2011; 7
Kaelin (10.1016/j.crphar.2021.100017_bib73) 2005; 5
Barnieh (10.1016/j.crphar.2021.100017_bib8) 2019; 79
Shi (10.1016/j.crphar.2021.100017_bib134) 2018; 432
Shiloh (10.1016/j.crphar.2021.100017_bib135) 2001; 83
Nagel (10.1016/j.crphar.2021.100017_bib104) 2019; 18
McMahon (10.1016/j.crphar.2021.100017_bib98) 1998; 94
Gorgoulis (10.1016/j.crphar.2021.100017_bib55) 2005; 434
Arris (10.1016/j.crphar.2021.100017_bib5) 2000; 43
Fokas (10.1016/j.crphar.2021.100017_bib44) 2012; 3
Gill (10.1016/j.crphar.2021.100017_bib52) 2014; 11
Sancar (10.1016/j.crphar.2021.100017_bib125) 2004; 73
Kumagai (10.1016/j.crphar.2021.100017_bib83) 2006; 124
Kim (10.1016/j.crphar.2021.100017_bib79) 2017; 140
Kwok (10.1016/j.crphar.2021.100017_bib85) 2015; 385
Sun (10.1016/j.crphar.2021.100017_bib138) 2007; 246
Abraham (10.1016/j.crphar.2021.100017_bib1) 2001; 15
Peasland (10.1016/j.crphar.2021.100017_bib113) 2011; 105
Xu (10.1016/j.crphar.2021.100017_bib159) 2011; 6
Jiang (10.1016/j.crphar.2021.100017_bib67) 2019; 11
Huntoon (10.1016/j.crphar.2021.100017_bib62) 2013; 73
Sprong (10.1016/j.crphar.2021.100017_bib137) 2006; 64
Gorecki (10.1016/j.crphar.2021.100017_bib54) 2020; 210
Foote (10.1016/j.crphar.2021.100017_bib46) 2013; 56
Pires (10.1016/j.crphar.2021.100017_bib114) 2010; 70
Bartkova (10.1016/j.crphar.2021.100017_bib13) 2005; 434
resTORbio (10.1016/j.crphar.2021.100017_bib121)
Gilad (10.1016/j.crphar.2021.100017_bib51) 2010; 70
Oliver (10.1016/j.crphar.2021.100017_bib111) 2010; 24
Alderton (10.1016/j.crphar.2021.100017_bib3) 2004; 13
Helt (10.1016/j.crphar.2021.100017_bib61) 2005; 280
Plummer (10.1016/j.crphar.2021.100017_bib117) 2018; 29
Bosotti (10.1016/j.crphar.2021.100017_bib19) 2000; 25
Marechal (10.1016/j.crphar.2021.100017_bib95) 2015; 25
O'Driscoll (10.1016/j.crphar.2021.100017_bib110) 2003; 33
Lavin (10.1016/j.crphar.2021.100017_bib86) 2008; 9
Thomas (10.1016/j.crphar.2021.100017_bib142) 2017; 36
National Cancer Institute Website (10.1016/j.crphar.2021.100017_bib105)
Liu (10.1016/j.crphar.2021.100017_bib90) 2011; 54
Jossé (10.1016/j.crphar.2021.100017_bib71) 2014; 74
Pires (10.1016/j.crphar.2021.100017_bib115) 2012; 107
Kaeberlein (10.1016/j.crphar.2021.100017_bib72) 2020; 4
Roos (10.1016/j.crphar.2021.100017_bib122) 2006; 12
Carlo (10.1016/j.crphar.2021.100017_bib26) 2016; 21
O'Carrigan (10.1016/j.crphar.2021.100017_bib109) 2016; 34
Sarkaria (10.1016/j.crphar.2021.100017_bib127) 1998; 58
Charrier (10.1016/j.crphar.2021.100017_bib28) 2011; 54
References_xml – volume: 421
  start-page: 499
  year: 2003
  end-page: 506
  ident: bib6
  article-title: DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
  publication-title: Nature
– volume: 21
  start-page: 4780
  year: 2015
  end-page: 4785
  ident: bib75
  article-title: Molecular pathways: targeting ATR in cancer therapy
  publication-title: Clin. Canc. Res.
– volume: 6
  start-page: 37
  year: 2015
  end-page: 41
  ident: bib9
  article-title: Structure-based drug design of novel potent and selective tetrahydropyrazolo[1,5-a]pyrazines as ATR inhibitors
  publication-title: ACS Med. Chem. Lett.
– volume: 316
  start-page: 1160
  year: 2007
  end-page: 1166
  ident: bib97
  article-title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
  publication-title: Science
– volume: 42
  start-page: 30
  year: 2016
  end-page: 40
  ident: bib155
  article-title: Breaking the DNA damage response to improve cervical cancer treatment
  publication-title: Canc. Treat Rev.
– volume: 12
  start-page: 323
  year: 2017
  end-page: 332
  ident: bib156
  article-title: A phase ib study of the dual PI3K/mTOR inhibitor dactolisib (BEZ235) combined with everolimus in patients with advanced solid malignancies
  publication-title: Targeted Oncol.
– volume: 10
  start-page: 275
  year: 2018
  ident: bib100
  article-title: The impact of p53 dysfunction in ATR inhibitor cytotoxicity and chemo- and Radiosensitisation
  publication-title: Cancers
– volume: 22
  start-page: 297
  year: 2008
  end-page: 302
  ident: bib144
  article-title: ATR signaling can drive cells into senescence in the absence of DNA breaks
  publication-title: Gene Dev.
– volume: 10
  year: 2015
  ident: bib141
  article-title: Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling
  publication-title: PloS One
– volume: 26
  year: 2015
  ident: bib31
  article-title: Abstract O6.3; ATR inhibitor AZD6738
  publication-title: Ann. Oncol.
– volume: 502
  start-page: 333
  year: 2013
  end-page: 339
  ident: bib74
  article-title: Mutational landscape and significance across 12 major cancer types
  publication-title: Nature
– volume: 122
  start-page: 241
  year: 2012
  end-page: 252
  ident: bib130
  article-title: Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR
  publication-title: J. Clin. Invest.
– volume: 56
  start-page: 2125
  year: 2013
  end-page: 2138
  ident: bib46
  article-title: Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-y l}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity
  publication-title: J. Med. Chem.
– volume: 79
  start-page: 2933
  year: 2019
  end-page: 2946
  ident: bib32
  article-title: Inhibition of ataxia-telangiectasia mutated and RAD3-related (ATR) overcomes oxaliplatin resistance and promotes antitumor immunity in colorectal cancer
  publication-title: Canc. Res.
– volume: 19
  start-page: 169
  year: 2004
  end-page: 185
  ident: bib35
  article-title: Endogenous DNA damage in humans: a review of quantitative data
  publication-title: Mutagenesis
– volume: 34
  year: 2016
  ident: bib116
  article-title: Phase I trial of first-in-class ATR inhibitor VX-970 in combination with gemcitabine (Gem) in advanced solid tumors (NCT02157792)
  publication-title: J. Clin. Oncol.
– volume: 70
  start-page: 9693
  year: 2010
  end-page: 9702
  ident: bib51
  article-title: Combining ATR suppression with oncogenic ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner
  publication-title: Canc. Res.
– volume: 77
  start-page: 3040
  year: 2017
  end-page: 3056
  ident: bib129
  article-title: ATM deficiency is associated with sensitivity to PARP1- and ATR inhibitors in lung adenocarcinoma
  publication-title: Canc. Res.
– volume: 3
  start-page: e441
  year: 2012
  ident: bib44
  article-title: Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation
  publication-title: Cell Death Dis.
– volume: 109
  start-page: 8230
  year: 2012
  end-page: 8235
  ident: bib77
  article-title: Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery
  publication-title: Proc. Natl. Acad. Sci. Unit. States Am.
– volume: 14
  start-page: 379
  year: 2013
  end-page: 389
  ident: bib157
  article-title: Chemotherapy induced DNA damage response Convergence of drugs and pathways
  publication-title: Canc. Biol. Ther.
– volume: 9
  start-page: 41
  year: 2017
  ident: bib123
  article-title: Targeting the ATR-CHK1 Axis in cancer therapy
  publication-title: Cancers
– volume: 43
  start-page: 2797
  year: 2000
  end-page: 2804
  ident: bib5
  article-title: Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles
  publication-title: J. Med. Chem.
– volume: 83
  start-page: 209
  year: 2001
  end-page: 254
  ident: bib135
  article-title: ATM: genome stability, neuronal development, and cancer cross paths
  publication-title: Adv. Canc. Res.
– volume: 34
  year: 2016
  ident: bib109
  article-title: Phase I trial of a first-in-class ATR inhibitor VX-970 as monotherapy (mono) or in combination (combo) with carboplatin (CP) incorporating pharmacodynamics (PD) studies
  publication-title: J. Clin. Oncol.
– volume: 17
  start-page: 615
  year: 2003
  end-page: 628
  ident: bib21
  article-title: Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance
  publication-title: Genes Dev.
– volume: 147
  start-page: 695
  year: 2017
  end-page: 704
  ident: bib16
  article-title: PARP inhibitors: clinical utility and possibilities of overcoming resistance
  publication-title: Gynecol. Oncol.
– volume: 76
  start-page: CT012
  year: 2016
  ident: bib132
  article-title: Abstract CT012: phase 1 trial of first-in-class ATR inhibitor VX-970 in combination with cisplatin (Cis) in patients (pts) with advanced solid tumors (NCT02157792)
  publication-title: Canc. Res.
– volume: 7
  start-page: 20
  year: 2017
  end-page: 37
  ident: bib22
  article-title: Targeting DNA repair in cancer: beyond PARP inhibitors
  publication-title: Canc. Discov.
– volume: 73
  year: 2013
  ident: bib56
  article-title: The pre-clinical in vitro and in vivo activity of AZD6738: a potent and selective inhibitor of ATR kinase
  publication-title: Canc. Res.
– volume: 79
  year: 2019
  ident: bib163
  article-title: Abstract 369: antitumor activity of M4344, a potent and selective ATR inhibitor, in monotherapy and combination therapy
  publication-title: Canc. Res.
– volume: 71
  start-page: 587
  year: 1992
  end-page: 597
  ident: bib78
  article-title: A mammalian-cell cycle checkpoint pathway utilizing P53 and Gadd45 is defective in ataxia-telangiectasia
  publication-title: Cell
– volume: 79
  start-page: 350
  year: 2019
  ident: bib8
  article-title: Abstract 350: investigating the mechanisms of cellular uptake and metabolism of ICT2588, an MT-MMP-activated prodrug
  publication-title: Canc. Res.
– volume: 16
  start-page: 25
  year: 2017
  end-page: 34
  ident: bib36
  article-title: Radiosensitization by the ATR inhibitor AZD6738 through generation of acentric micronuclei
  publication-title: Mol. Canc. Therapeut.
– volume: 69
  year: 2016
  ident: bib162
  article-title: 1LBA - phase I modular study of AZD6738, a novel oral, potent and selective ataxia telangiectasia Rad3-related (ATR) inhibitor in combination (combo) with carboplatin, olaparib or durvalumab in patients (pts) with advanced cancers
  publication-title: Eur. J. Canc.
– volume: 11
  start-page: 220
  year: 2010
  end-page: 228
  ident: bib106
  article-title: Genomic instability--an evolving hallmark of cancer
  publication-title: Nat. Rev. Mol. Cell Biol.
– volume: 17
  start-page: 2462
  year: 2018
  ident: bib146
  article-title: ATR inhibition is a promising radiosensitizing strategy for triple-negative breast cancer
  publication-title: Mol. Canc. Therapeut.
– volume: 2
  start-page: 196
  year: 2001
  end-page: 206
  ident: bib147
  article-title: Chromosomal stability and the DNA double-stranded break connection
  publication-title: Nat. Rev. Genet.
– volume: 74
  start-page: 6968
  year: 2014
  ident: bib71
  article-title: ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase I inhibitors by disabling DNA replication initiation and fork elongation responses
  publication-title: Canc. Res.
– volume: 18
  start-page: 1331
  year: 2011
  end-page: 1338
  ident: bib102
  article-title: Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors
  publication-title: Nat. Struct. Mol. Biol.
– volume: 100
  start-page: 57
  year: 2000
  end-page: 70
  ident: bib59
  article-title: The hallmarks of cancer
  publication-title: Cell
– volume: 6
  year: 2011
  ident: bib159
  article-title: Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo
  publication-title: PloS One
– volume: 164
  start-page: 273
  year: 2019
  end-page: 282
  ident: bib119
  article-title: Inhibition of Wee1 sensitizes AML cells to ATR inhibitor VE-822-induced DNA damage and apoptosis
  publication-title: Biochem. Pharmacol.
– volume: 7
  start-page: 873
  year: 2015
  end-page: 891
  ident: bib47
  article-title: Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer
  publication-title: Future Med. Chem.
– volume: 145
  start-page: 435
  year: 2011
  end-page: 446
  ident: bib15
  article-title: Nucleotide deficiency promotes genomic instability in early stages of cancer development
  publication-title: Cell
– volume: 20
  start-page: 478
  year: 2018
  end-page: 488
  ident: bib68
  article-title: Combined inhibition of ATR and WEE1 as a novel therapeutic strategy in triple-negative breast cancer
  publication-title: Neoplasia
– volume: 31
  start-page: 1661
  year: 2012
  end-page: 1672
  ident: bib41
  article-title: Efficacy of CHK inhibitors as single agents in MYC-driven lymphoma cells
  publication-title: Oncogene
– volume: 61
  start-page: 9889
  year: 2018
  end-page: 9907
  ident: bib48
  article-title: Discovery and characterization of AZD6738, a potent inhibitor of ataxia telangiectasia mutated and Rad3 related (ATR) kinase with application as an anticancer agent
  publication-title: J. Med. Chem.
– volume: 58
  start-page: 4375
  year: 1998
  end-page: 4382
  ident: bib127
  article-title: Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin
  publication-title: Canc. Res.
– volume: 128
  start-page: 3926
  year: 2018
  end-page: 3940
  ident: bib149
  article-title: ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation
  publication-title: J. Clin. Invest.
– volume: 14
  start-page: 397
  year: 2000
  end-page: 402
  ident: bib20
  article-title: ATR disruption leads to chromosomal fragmentation and early embryonic lethality
  publication-title: Genes Dev.
– volume: 10
  start-page: 213
  year: 2016
  end-page: 223
  ident: bib4
  article-title: Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer
  publication-title: Mol. Oncol.
– volume: 277
  start-page: 1497
  year: 1997
  end-page: 1501
  ident: bib126
  article-title: Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25
  publication-title: Science
– volume: 178
  start-page: 193
  year: 2018
  end-page: 203
  ident: bib29
  article-title: Biodegradable PEG-poly(ω-pentadecalactone-co-p-dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors
  publication-title: Biomaterials
– volume: 14
  start-page: PR14
  year: 2015
  ident: bib161
  article-title: Abstract PR14: phase I trial of first-in-class ataxia telangiectasia-mutated and Rad3-related (ATR) inhibitor VX-970 as monotherapy (mono) or in combination with carboplatin (CP) in advanced cancer patients (pts) with preliminary evidence of target modulation and antitumor activity
  publication-title: Mol. Canc. Therapeut.
– volume: 9
  start-page: 2361
  year: 1998
  end-page: 2374
  ident: bib50
  article-title: Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity
  publication-title: Mol. Biol. Cell
– volume: 18
  start-page: 721
  year: 2011
  end-page: 727
  ident: bib145
  article-title: A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations
  publication-title: Nat. Struct. Mol. Biol.
– volume: 140
  start-page: 109
  year: 2017
  end-page: 119
  ident: bib79
  article-title: Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells
  publication-title: Int. J. Canc.
– volume: 22
  start-page: 1834
  year: 2002
  end-page: 1843
  ident: bib58
  article-title: Hypoxia links ATR and p53 through replication arrest
  publication-title: Mol. Cell Biol.
– volume: 13
  start-page: 738
  year: 2001
  end-page: 747
  ident: bib11
  article-title: Mammalian G1- and S-phase checkpoints in response to DNA damage
  publication-title: Curr. Opin. Cell Biol.
– year: 2019
  ident: bib121
– volume: 434
  start-page: 917
  year: 2005
  end-page: 921
  ident: bib38
  article-title: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
  publication-title: Nature
– volume: 13
  start-page: 1072
  year: 2012
  end-page: 1081
  ident: bib118
  article-title: The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy
  publication-title: Canc. Biol. Ther.
– volume: 22
  start-page: 4163
  year: 2012
  end-page: 4168
  ident: bib42
  article-title: Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor
  publication-title: Bioorg. Med. Chem. Lett
– volume: 434
  start-page: 864
  year: 2005
  end-page: 870
  ident: bib13
  article-title: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
  publication-title: Nature
– volume: 280
  start-page: 15158
  year: 2005
  end-page: 15164
  ident: bib40
  article-title: DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATM
  publication-title: J. Biol. Chem.
– volume: 13
  start-page: 3127
  year: 2004
  end-page: 3138
  ident: bib3
  article-title: Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway
  publication-title: Hum. Mol. Genet.
– volume: 41
  start-page: 1013
  year: 2005
  end-page: 1020
  ident: bib17
  article-title: The ATM/p53 pathway is commonly targeted for inactivation in squamous cell carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms
  publication-title: Oral Oncol.
– volume: 36
  start-page: 713
  year: 2016
  end-page: 719
  ident: bib39
  article-title: A phase II study of BEZ235 in patients with everolimus-resistant, advanced pancreatic neuroendocrine tumours
  publication-title: Anticancer Res.
– volume: 210
  start-page: 107518
  year: 2020
  ident: bib54
  article-title: Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): clinical candidate for cancer therapy
  publication-title: Pharmacol. Ther.
– volume: 432
  start-page: 56
  year: 2018
  end-page: 68
  ident: bib134
  article-title: The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma
  publication-title: Canc. Lett.
– volume: 107
  start-page: 291
  year: 2012
  end-page: 299
  ident: bib115
  article-title: Targeting radiation-resistant hypoxic tumour cells through ATR inhibition
  publication-title: Br. J. Canc.
– volume: 18
  start-page: 762
  year: 2019
  ident: bib104
  article-title: Inhibition of the replication stress response is a synthetic vulnerability in SCLC that acts synergistically in combination with cisplatin
  publication-title: Mol. Canc. Therapeut.
– volume: 36
  start-page: 1594
  year: 2018
  end-page: 1602
  ident: bib143
  article-title: Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors
  publication-title: J. Clin. Oncol.
– volume: 25
  start-page: 225
  year: 2000
  end-page: 227
  ident: bib19
  article-title: FAT: a novel domain in PIK-related kinases
  publication-title: Trends Biochem. Sci.
– volume: 68
  start-page: 1636
  year: 2005
  end-page: 1644
  ident: bib76
  article-title: Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival
  publication-title: Mol. Pharmacol.
– volume: 70
  start-page: 925
  year: 2010
  end-page: 935
  ident: bib114
  article-title: Effects of acute versus chronic Hypoxia on DNA damage responses and genomic instability
  publication-title: Canc. Res.
– volume: 3
  start-page: 247
  year: 2003
  end-page: 258
  ident: bib136
  article-title: Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A
  publication-title: Canc. Cell
– volume: 10
  start-page: 8
  year: 2020
  ident: bib99
  article-title: ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion
  publication-title: Cell Biosci.
– volume: 385
  start-page: S58
  year: 2015
  ident: bib85
  article-title: Synthetic lethality in chronic lymphocytic leukaemia with DNA damage response defects by targeting the ATR pathway
  publication-title: Lancet
– volume: 54
  start-page: 2320
  year: 2011
  end-page: 2330
  ident: bib28
  article-title: Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents
  publication-title: J. Med. Chem.
– volume: 60
  start-page: 139
  year: 2017
  end-page: 151
  ident: bib27
  article-title: DNA damage response inhibitors: mechanisms and potential applications in cancer therapy
  publication-title: Canc. Treat Rev.
– volume: 124
  year: 2006
  ident: bib83
  article-title: TopBP1 activates the ATR-ATRIP complex
  publication-title: Cell
– volume: 8
  start-page: 1307
  year: 2018
  end-page: 1316
  ident: bib139
  article-title: Inhibition of ATR downregulates PD-L1 and sensitizes tumor cells to T cell-mediated killing
  publication-title: Am. J. Cancer Res.
– volume: 281
  start-page: 9346
  year: 2006
  end-page: 9350
  ident: bib103
  article-title: Rapid activation of ATR by ionizing radiation requires ATM and Mre11
  publication-title: J. Biol. Chem.
– volume: 444
  start-page: 633
  year: 2006
  end-page: 637
  ident: bib14
  article-title: Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
  publication-title: Nature
– volume: 11
  start-page: 4371
  year: 2019
  end-page: 4390
  ident: bib67
  article-title: Current status and future prospects of PARP inhibitor clinical trials in ovarian cancer
  publication-title: Canc. Manag. Res.
– volume: 149
  start-page: 124
  year: 2015
  end-page: 138
  ident: bib153
  article-title: ATM and ATR as therapeutic targets in cancer
  publication-title: Pharmacol. Therapeut.
– volume: 19
  start-page: 26
  year: 2020
  end-page: 38
  ident: bib154
  article-title: The novel ATR inhibitor BAY 1895344 is efficacious as monotherapy and combined with DNA damage–inducing or repair–compromising therapies in preclinical cancer models
  publication-title: Mol. Canc. Therapeut.
– volume: 121
  start-page: 232
  year: 2016
  end-page: 238
  ident: bib88
  article-title: Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer
  publication-title: Radiother. Oncol.
– volume: 21
  start-page: 787
  year: 2016
  end-page: 788
  ident: bib26
  article-title: A phase ib study of BEZ235, a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), in patients with advanced renal cell carcinoma
  publication-title: Oncol.
– volume: 28
  start-page: 5736
  year: 2008
  end-page: 5746
  ident: bib131
  article-title: A novel Tel1/ATM N-terminal motif, TAN, is essential for telomere length maintenance and a DNA damage response
  publication-title: Mol. Cell Biol.
– volume: 9
  year: 2008
  ident: bib86
  article-title: Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
  publication-title: Nat. Rev. Mol. Cell Biol.
– volume: 20
  start-page: 1803
  year: 2001
  end-page: 1815
  ident: bib140
  article-title: Regulation of the G2/M transition by p53
  publication-title: Oncogene
– volume: 37
  start-page: 5678
  year: 2009
  end-page: 5689
  ident: bib108
  article-title: Inhibition of ATR protein kinase activity by schisandrin B in DNA damage response
  publication-title: Nucleic Acids Res.
– volume: 17
  start-page: 1670
  year: 2018
  end-page: 1682
  ident: bib151
  article-title: The ATR inhibitor AZD6738 synergizes with gemcitabine in vitro and in vivo to induce pancreatic ductal adenocarcinoma regression
  publication-title: Mol. Canc. Therapeut.
– volume: 59
  start-page: 4375
  year: 1999
  end-page: 4382
  ident: bib128
  article-title: Inhibition of ATM and ATR kinase activities by the radiosensitizing agent
  publication-title: Caffeine. Cancer Res
– volume: 129
  start-page: 1329
  year: 2019
  end-page: 1344
  ident: bib24
  article-title: Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis
  publication-title: J. Clin. Invest.
– volume: 246
  start-page: 300
  year: 2007
  end-page: 307
  ident: bib138
  article-title: A dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1
  publication-title: Canc. Lett.
– volume: 7
  year: 2012
  ident: bib91
  article-title: Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition
  publication-title: PloS One
– volume: 9
  start-page: 616
  year: 2008
  end-page: 627
  ident: bib30
  article-title: ATR: an essential regulator of genome integrity
  publication-title: Nat. Rev. Mol. Cell Biol.
– volume: 294
  start-page: 1713
  year: 2001
  end-page: 1716
  ident: bib33
  article-title: ATR and ATRIP: partners in checkpoint signaling
  publication-title: Science
– volume: 46
  start-page: 50
  year: 2012
  end-page: 60
  ident: bib53
  article-title: Schisandrin B, attenuates cisplatin-induced oxidative stress, genotoxicity and neurotoxicity through modulating NF-kappaB pathway in mice
  publication-title: Free Radic. Res.
– volume: 6
  start-page: 44289
  year: 2015
  end-page: 44305
  ident: bib148
  article-title: The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo
  publication-title: Oncotarget
– volume: 78
  year: 2018
  ident: bib82
  article-title: Abstract CT026: phase I study of AZD6738, an inhibitor of ataxia telangiectasia Rad3-related (ATR), in combination with olaparib or durvalumab in patients (pts) with advanced solid cancers
  publication-title: Canc. Res.
– volume: 32
  start-page: 308
  year: 2011
  end-page: 316
  ident: bib49
  article-title: Anticancer therapy with checkpoint inhibitors: what, where and when?
  publication-title: Trends Pharmacol. Sci.
– volume: 73
  year: 2013
  ident: bib70
  article-title: Discovery of AZD6738, a potent and selective inhibitor with the potential to test the clinical efficacy of ATR kinase inhibition in cancer patients
  publication-title: Canc. Res.
– volume: 434
  start-page: 913
  year: 2005
  end-page: 917
  ident: bib23
  article-title: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
  publication-title: Nature
– volume: 281
  start-page: 1677
  year: 1998
  end-page: 1679
  ident: bib25
  article-title: Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
  publication-title: Science
– volume: 62
  year: 2019
  ident: bib80
  article-title: Rational design of 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine (VX-970, M6620): optimization of intra- and intermolecular polar interactions of a new ataxia telangiectasia mutated and Rad3-related (ATR) kinase inhibitor
  publication-title: J. Med. Chem.
– volume: 7
  start-page: 1851
  year: 2008
  end-page: 1863
  ident: bib94
  article-title: Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
  publication-title: Mol. Canc. Therapeut.
– volume: 25
  start-page: 9
  year: 2015
  end-page: 23
  ident: bib95
  article-title: RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response
  publication-title: Cell Res.
– volume: 73
  start-page: 2574
  year: 2013
  end-page: 2586
  ident: bib92
  article-title: Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR
  publication-title: Canc. Res.
– volume: 105
  start-page: 372
  year: 2011
  end-page: 381
  ident: bib113
  article-title: Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines
  publication-title: Br. J. Canc.
– volume: 3
  start-page: 1311
  year: 2010
  end-page: 1334
  ident: bib150
  article-title: Prospects for the use of ATR inhibitors to treat cancer
  publication-title: Pharmaceuticals
– volume: 3
  start-page: 763
  year: 2004
  end-page: 772
  ident: bib63
  article-title: Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling
  publication-title: Mol. Canc. Therapeut.
– volume: 5
  start-page: 689
  year: 2005
  end-page: 698
  ident: bib73
  article-title: The concept of synthetic lethality in the context of anticancer therapy
  publication-title: Nat. Rev. Canc.
– volume: 280
  start-page: 1186
  year: 2005
  end-page: 1192
  ident: bib61
  article-title: Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage
  publication-title: J. Biol. Chem.
– volume: 1
  start-page: 113
  year: 2007
  end-page: 126
  ident: bib124
  article-title: Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss
  publication-title: Cell stem cell
– volume: 25
  start-page: 3392
  year: 2019
  ident: bib37
  article-title: ATR inhibition potentiates the radiation-induced inflammatory tumor microenvironment
  publication-title: Clin. Canc. Res.
– volume: 5
  start-page: 5674
  year: 2014
  end-page: 5685
  ident: bib57
  article-title: Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970
  publication-title: Oncotarget
– volume: 69
  start-page: 7644
  year: 2009
  end-page: 7652
  ident: bib81
  article-title: Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations
  publication-title: Canc. Res.
– volume: 96
  start-page: 11
  year: 2007
  end-page: 15
  ident: bib89
  article-title: Cancer risks among BRCA1 and BRCA2 mutation carriers
  publication-title: Br. J. Canc.
– volume: 16
  start-page: 566
  year: 2017
  end-page: 577
  ident: bib101
  article-title: AZD6738, A novel oral inhibitor of ATR, induces synthetic lethality with ATM deficiency in gastric cancer cells
  publication-title: Mol. Canc. Therapeut.
– volume: 361
  start-page: 123
  year: 2009
  end-page: 134
  ident: bib45
  article-title: Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers
  publication-title: N. Engl. J. Med.
– volume: 23
  start-page: 1895
  year: 2009
  end-page: 1909
  ident: bib66
  article-title: The combined status of ATM and p53 link tumor development with therapeutic response
  publication-title: Gene Dev.
– volume: 12
  start-page: 440
  year: 2006
  end-page: 450
  ident: bib122
  article-title: DNA damage-induced cell death by apoptosis
  publication-title: Trends Mol. Med.
– volume: 11
  start-page: 1294
  year: 2014
  end-page: 1300
  ident: bib52
  article-title: Tumor-targeted prodrug ICT2588 demonstrates therapeutic activity against solid tumors and reduced potential for cardiovascular toxicity
  publication-title: Mol. Pharm.
– volume: 23
  start-page: 882
  year: 2018
  end-page: 897
  ident: bib160
  article-title: A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening
  publication-title: Cell stem cell
– volume: 65
  year: 2018
  ident: bib84
  article-title: Initial testing (stage 1) of M6620 (formerly VX-970), a novel ATR inhibitor, alone and combined with cisplatin and melphalan, by the Pediatric Preclinical Testing Program
  publication-title: Pediatr. Blood Canc.
– volume: 36
  start-page: 133
  year: 2011
  end-page: 140
  ident: bib43
  article-title: ATR: a master conductor of cellular responses to DNA replication stress
  publication-title: Trends Biochem. Sci.
– volume: 24
  start-page: 837
  year: 2010
  end-page: 852
  ident: bib111
  article-title: Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer
  publication-title: Gene Dev.
– volume: 6
  start-page: 42
  year: 2015
  end-page: 46
  ident: bib10
  article-title: Structure-based drug design of novel, potent, and selective azabenzimidazoles (ABI) as ATR inhibitors
  publication-title: ACS Med. Chem. Lett.
– volume: 36
  start-page: 1594
  year: 2017
  end-page: 1602
  ident: bib142
  article-title: Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors
  publication-title: J. Clin.l Oncol.
– volume: 73
  start-page: 3683
  year: 2013
  end-page: 3691
  ident: bib62
  article-title: ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status
  publication-title: Canc. Res.
– volume: 383
  start-page: 41
  year: 2016
  end-page: 52
  ident: bib96
  article-title: Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells to Chk1 inhibitor monotherapy
  publication-title: Canc. Lett.
– volume: 110
  start-page: 1064
  year: 2019
  end-page: 1075
  ident: bib152
  article-title: Pharmacologic characterization of fluzoparib, a novel poly (ADP-ribose) polymerase inhibitor undergoing clinical trials
  publication-title: Canc. Sci.
– volume: 7
  start-page: 428
  year: 2011
  end-page: 430
  ident: bib120
  article-title: Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR
  publication-title: Nat. Chem. Biol.
– volume: 444
  start-page: 756
  year: 2006
  end-page: 760
  ident: bib7
  article-title: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
  publication-title: Nature
– volume: 94
  start-page: 363
  year: 1998
  end-page: 374
  ident: bib98
  article-title: The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins
  publication-title: Cell
– ident: bib105
– volume: 434
  start-page: 907
  year: 2005
  end-page: 913
  ident: bib55
  article-title: Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
  publication-title: Nature
– volume: 52
  start-page: 17
  year: 2016
  end-page: 28
  ident: bib18
  article-title: Olaparib for the treatment of ovarian cancer
  publication-title: Drugs Today
– volume: 461
  start-page: 1071
  year: 2009
  end-page: 1078
  ident: bib64
  article-title: The DNA-damage response in human biology and disease
  publication-title: Nature
– volume: 54
  start-page: 1473
  year: 2011
  end-page: 1480
  ident: bib90
  article-title: Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl) benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer
  publication-title: J. Med. Chem.
– volume: 29
  start-page: viii519
  year: 2018
  ident: bib117
  article-title: Phase I dose expansion data for M6620 (formerly VX-970), a first-in-class ATR inhibitor, combined with gemcitabine (Gem) in patients (pts) with advanced non-small cell lung cancer (NSCLC)
  publication-title: Ann. Oncol.
– volume: 12
  start-page: 149
  year: 2016
  end-page: 151
  ident: bib69
  article-title: Olaparib recommendations for ovarian cancer patients
  publication-title: Future Oncol.
– volume: 28
  start-page: 3067
  year: 2009
  end-page: 3073
  ident: bib87
  article-title: Emerging common themes in regulation of PIKKs and PI3Ks
  publication-title: EMBO J.
– volume: 64
  start-page: 562
  year: 2006
  end-page: 572
  ident: bib137
  article-title: Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status
  publication-title: Int. J. Radiat. Oncol. Biol. Phys.
– volume: 15
  start-page: 2177
  year: 2001
  end-page: 2196
  ident: bib1
  article-title: Cell cycle checkpoint signaling through the ATM and ATR kinases
  publication-title: Genes Dev.
– volume: 98
  start-page: 9092
  year: 2001
  end-page: 9097
  ident: bib107
  article-title: ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation
  publication-title: Proc. Natl. Acad. Sci. Unit. States Am.
– volume: 33
  start-page: 497
  year: 2003
  end-page: 501
  ident: bib110
  article-title: A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome
  publication-title: Nat. Genet.
– volume: 144
  start-page: 646
  year: 2011
  end-page: 674
  ident: bib60
  article-title: Hallmarks of cancer: the next generation
  publication-title: Cell
– volume: 4
  start-page: 32
  year: 2020
  end-page: 34
  ident: bib72
  article-title: RTB101 and immune function in the elderly: interpreting an unsuccessful clinical trial
  publication-title: Transl. Med. Aging
– volume: 77
  year: 2017
  ident: bib93
  article-title: Abstract 983: identification of potent, highly selective and orally available ATR inhibitor BAY 1895344 with favorable PK properties and promising efficacy in monotherapy and combination in preclinical tumor models
  publication-title: Canc. Res.
– volume: 6
  start-page: 648
  year: 2004
  end-page: 655
  ident: bib133
  article-title: ATR and ATM regulate the timing of DNA replication origin firing
  publication-title: Nat. Cell Biol.
– volume: 73
  start-page: 39
  year: 2004
  end-page: 85
  ident: bib125
  article-title: Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints
  publication-title: Annu.l Rev. Biochem.
– volume: 37
  year: 2019
  ident: bib34
  article-title: First-in-human trial of the oral ataxia telangiectasia and Rad3-related (ATR) inhibitor BAY 1895344 in patients (pts) with advanced solid tumors
  publication-title: J. Clin. Oncol.
– volume: 278
  start-page: 21767
  year: 2003
  end-page: 21773
  ident: bib158
  article-title: Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents
  publication-title: J. Biol. Chem.
– volume: 169
  start-page: 277
  year: 2018
  end-page: 286
  ident: bib2
  article-title: Targeting ataxia telangiectasia-mutated- and Rad3-related kinase (ATR) in PTEN-deficient breast cancers for personalized therapy
  publication-title: Breast Canc. Res. Treat.
– volume: 3
  start-page: 421
  year: 2003
  end-page: 429
  ident: bib12
  article-title: Chk1 and Chk2 kinases in checkpoint control and cancer
  publication-title: Canc. Cell
– volume: 72
  year: 2012
  ident: bib65
  article-title: Abstract 1823: AZ20, a novel potent and selective inhibitor of ATR kinase with in vivo antitumour activity
  publication-title: Canc. Res.
– volume: 104
  start-page: 2807
  year: 2005
  end-page: 2816
  ident: bib112
  article-title: BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases
  publication-title: Cancer
– volume: 34
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib116
  article-title: Phase I trial of first-in-class ATR inhibitor VX-970 in combination with gemcitabine (Gem) in advanced solid tumors (NCT02157792)
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2016.34.15_suppl.2513
– volume: 83
  start-page: 209
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib135
  article-title: ATM: genome stability, neuronal development, and cancer cross paths
  publication-title: Adv. Canc. Res.
  doi: 10.1016/S0065-230X(01)83007-4
– volume: 110
  start-page: 1064
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib152
  article-title: Pharmacologic characterization of fluzoparib, a novel poly (ADP-ribose) polymerase inhibitor undergoing clinical trials
  publication-title: Canc. Sci.
  doi: 10.1111/cas.13947
– volume: 69
  start-page: 7644
  year: 2009
  ident: 10.1016/j.crphar.2021.100017_bib81
  article-title: Dual phosphoinositide 3-kinase/mammalian target of rapamycin blockade is an effective radiosensitizing strategy for the treatment of non-small cell lung cancer harboring K-RAS mutations
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-09-0823
– volume: 210
  start-page: 107518
  year: 2020
  ident: 10.1016/j.crphar.2021.100017_bib54
  article-title: Discovery of ATR kinase inhibitor berzosertib (VX-970, M6620): clinical candidate for cancer therapy
  publication-title: Pharmacol. Ther.
  doi: 10.1016/j.pharmthera.2020.107518
– volume: 20
  start-page: 1803
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib140
  article-title: Regulation of the G2/M transition by p53
  publication-title: Oncogene
  doi: 10.1038/sj.onc.1204252
– volume: 25
  start-page: 225
  year: 2000
  ident: 10.1016/j.crphar.2021.100017_bib19
  article-title: FAT: a novel domain in PIK-related kinases
  publication-title: Trends Biochem. Sci.
  doi: 10.1016/S0968-0004(00)01563-2
– volume: 15
  start-page: 2177
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib1
  article-title: Cell cycle checkpoint signaling through the ATM and ATR kinases
  publication-title: Genes Dev.
  doi: 10.1101/gad.914401
– volume: 434
  start-page: 864
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib13
  article-title: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis
  publication-title: Nature
  doi: 10.1038/nature03482
– volume: 145
  start-page: 435
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib15
  article-title: Nucleotide deficiency promotes genomic instability in early stages of cancer development
  publication-title: Cell
  doi: 10.1016/j.cell.2011.03.044
– volume: 72
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib65
  article-title: Abstract 1823: AZ20, a novel potent and selective inhibitor of ATR kinase with in vivo antitumour activity
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2012-1823
– volume: 3
  start-page: 1311
  year: 2010
  ident: 10.1016/j.crphar.2021.100017_bib150
  article-title: Prospects for the use of ATR inhibitors to treat cancer
  publication-title: Pharmaceuticals
  doi: 10.3390/ph3051311
– volume: 20
  start-page: 478
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib68
  article-title: Combined inhibition of ATR and WEE1 as a novel therapeutic strategy in triple-negative breast cancer
  publication-title: Neoplasia
  doi: 10.1016/j.neo.2018.03.003
– volume: 21
  start-page: 4780
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib75
  article-title: Molecular pathways: targeting ATR in cancer therapy
  publication-title: Clin. Canc. Res.
  doi: 10.1158/1078-0432.CCR-15-0479
– volume: 9
  start-page: 2361
  year: 1998
  ident: 10.1016/j.crphar.2021.100017_bib50
  article-title: Characterization of ATM expression, localization, and associated DNA-dependent protein kinase activity
  publication-title: Mol. Biol. Cell
  doi: 10.1091/mbc.9.9.2361
– volume: 280
  start-page: 1186
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib61
  article-title: Ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein exhibit selective target specificities in response to different forms of DNA damage
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M410873200
– volume: 104
  start-page: 2807
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib112
  article-title: BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases
  publication-title: Cancer
  doi: 10.1002/cncr.21536
– volume: 77
  start-page: 3040
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib129
  article-title: ATM deficiency is associated with sensitivity to PARP1- and ATR inhibitors in lung adenocarcinoma
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-16-3398
– volume: 124
  year: 2006
  ident: 10.1016/j.crphar.2021.100017_bib83
  article-title: TopBP1 activates the ATR-ATRIP complex
  publication-title: Cell
  doi: 10.1016/j.cell.2005.12.041
– volume: 6
  start-page: 42
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib10
  article-title: Structure-based drug design of novel, potent, and selective azabenzimidazoles (ABI) as ATR inhibitors
  publication-title: ACS Med. Chem. Lett.
  doi: 10.1021/ml500352s
– volume: 37
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib34
  article-title: First-in-human trial of the oral ataxia telangiectasia and Rad3-related (ATR) inhibitor BAY 1895344 in patients (pts) with advanced solid tumors
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2019.37.15_suppl.3007
– volume: 6
  start-page: 648
  year: 2004
  ident: 10.1016/j.crphar.2021.100017_bib133
  article-title: ATR and ATM regulate the timing of DNA replication origin firing
  publication-title: Nat. Cell Biol.
  doi: 10.1038/ncb1145
– volume: 5
  start-page: 5674
  year: 2014
  ident: 10.1016/j.crphar.2021.100017_bib57
  article-title: Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.2158
– volume: 105
  start-page: 372
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib113
  article-title: Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines
  publication-title: Br. J. Canc.
  doi: 10.1038/bjc.2011.243
– volume: 246
  start-page: 300
  year: 2007
  ident: 10.1016/j.crphar.2021.100017_bib138
  article-title: A dual inhibitor of P-glycoprotein and multidrug resistance-associated protein 1
  publication-title: Canc. Lett.
  doi: 10.1016/j.canlet.2006.03.009
– volume: 70
  start-page: 925
  year: 2010
  ident: 10.1016/j.crphar.2021.100017_bib114
  article-title: Effects of acute versus chronic Hypoxia on DNA damage responses and genomic instability
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-09-2715
– volume: 36
  start-page: 1594
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib143
  article-title: Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2017.76.6915
– volume: 19
  start-page: 26
  year: 2020
  ident: 10.1016/j.crphar.2021.100017_bib154
  article-title: The novel ATR inhibitor BAY 1895344 is efficacious as monotherapy and combined with DNA damage–inducing or repair–compromising therapies in preclinical cancer models
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-19-0019
– volume: 14
  start-page: 397
  year: 2000
  ident: 10.1016/j.crphar.2021.100017_bib20
  article-title: ATR disruption leads to chromosomal fragmentation and early embryonic lethality
  publication-title: Genes Dev.
  doi: 10.1101/gad.14.4.397
– volume: 16
  start-page: 25
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib36
  article-title: Radiosensitization by the ATR inhibitor AZD6738 through generation of acentric micronuclei
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-16-0239
– volume: 70
  start-page: 9693
  year: 2010
  ident: 10.1016/j.crphar.2021.100017_bib51
  article-title: Combining ATR suppression with oncogenic ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-10-2286
– volume: 21
  start-page: 787
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib26
  article-title: A phase ib study of BEZ235, a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), in patients with advanced renal cell carcinoma
  publication-title: Oncol.
  doi: 10.1634/theoncologist.2016-0145
– volume: 36
  start-page: 133
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib43
  article-title: ATR: a master conductor of cellular responses to DNA replication stress
  publication-title: Trends Biochem. Sci.
  doi: 10.1016/j.tibs.2010.09.005
– volume: 65
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib84
  article-title: Initial testing (stage 1) of M6620 (formerly VX-970), a novel ATR inhibitor, alone and combined with cisplatin and melphalan, by the Pediatric Preclinical Testing Program
  publication-title: Pediatr. Blood Canc.
  doi: 10.1002/pbc.26825
– volume: 316
  start-page: 1160
  year: 2007
  ident: 10.1016/j.crphar.2021.100017_bib97
  article-title: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage
  publication-title: Science
  doi: 10.1126/science.1140321
– volume: 434
  start-page: 917
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib38
  article-title: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
  publication-title: Nature
  doi: 10.1038/nature03445
– volume: 61
  start-page: 9889
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib48
  article-title: Discovery and characterization of AZD6738, a potent inhibitor of ataxia telangiectasia mutated and Rad3 related (ATR) kinase with application as an anticancer agent
  publication-title: J. Med. Chem.
  doi: 10.1021/acs.jmedchem.8b01187
– volume: 11
  start-page: 1294
  year: 2014
  ident: 10.1016/j.crphar.2021.100017_bib52
  article-title: Tumor-targeted prodrug ICT2588 demonstrates therapeutic activity against solid tumors and reduced potential for cardiovascular toxicity
  publication-title: Mol. Pharm.
  doi: 10.1021/mp400760b
– volume: 36
  start-page: 1594
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib142
  article-title: Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors
  publication-title: J. Clin.l Oncol.
  doi: 10.1200/JCO.2017.76.6915
– volume: 22
  start-page: 1834
  year: 2002
  ident: 10.1016/j.crphar.2021.100017_bib58
  article-title: Hypoxia links ATR and p53 through replication arrest
  publication-title: Mol. Cell Biol.
  doi: 10.1128/MCB.22.6.1834-1843.2002
– volume: 96
  start-page: 11
  year: 2007
  ident: 10.1016/j.crphar.2021.100017_bib89
  article-title: Cancer risks among BRCA1 and BRCA2 mutation carriers
  publication-title: Br. J. Canc.
  doi: 10.1038/sj.bjc.6603535
– volume: 3
  start-page: e441
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib44
  article-title: Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation
  publication-title: Cell Death Dis.
  doi: 10.1038/cddis.2012.181
– volume: 18
  start-page: 1331
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib102
  article-title: Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors
  publication-title: Nat. Struct. Mol. Biol.
  doi: 10.1038/nsmb.2189
– volume: 140
  start-page: 109
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib79
  article-title: Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells
  publication-title: Int. J. Canc.
  doi: 10.1002/ijc.30373
– volume: 77
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib93
  article-title: Abstract 983: identification of potent, highly selective and orally available ATR inhibitor BAY 1895344 with favorable PK properties and promising efficacy in monotherapy and combination in preclinical tumor models
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2017-983
– volume: 7
  start-page: 20
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib22
  article-title: Targeting DNA repair in cancer: beyond PARP inhibitors
  publication-title: Canc. Discov.
  doi: 10.1158/2159-8290.CD-16-0860
– volume: 24
  start-page: 837
  year: 2010
  ident: 10.1016/j.crphar.2021.100017_bib111
  article-title: Chronic cisplatin treatment promotes enhanced damage repair and tumor progression in a mouse model of lung cancer
  publication-title: Gene Dev.
  doi: 10.1101/gad.1897010
– volume: 74
  start-page: 6968
  year: 2014
  ident: 10.1016/j.crphar.2021.100017_bib71
  article-title: ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase I inhibitors by disabling DNA replication initiation and fork elongation responses
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-13-3369
– volume: 10
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib141
  article-title: Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling
  publication-title: PloS One
  doi: 10.1371/journal.pone.0119214
– volume: 26
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib31
  article-title: Abstract O6.3; ATR inhibitor AZD6738
  publication-title: Ann. Oncol.
  doi: 10.1093/annonc/mdv084.3
– volume: 10
  start-page: 275
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib100
  article-title: The impact of p53 dysfunction in ATR inhibitor cytotoxicity and chemo- and Radiosensitisation
  publication-title: Cancers
  doi: 10.3390/cancers10080275
– volume: 144
  start-page: 646
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib60
  article-title: Hallmarks of cancer: the next generation
  publication-title: Cell
  doi: 10.1016/j.cell.2011.02.013
– volume: 385
  start-page: S58
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib85
  article-title: Synthetic lethality in chronic lymphocytic leukaemia with DNA damage response defects by targeting the ATR pathway
  publication-title: Lancet
  doi: 10.1016/S0140-6736(15)60373-7
– volume: 94
  start-page: 363
  year: 1998
  ident: 10.1016/j.crphar.2021.100017_bib98
  article-title: The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins
  publication-title: Cell
  doi: 10.1016/S0092-8674(00)81479-8
– volume: 3
  start-page: 763
  year: 2004
  ident: 10.1016/j.crphar.2021.100017_bib63
  article-title: Molecular pharmacology and antitumor activity of PX-866, a novel inhibitor of phosphoinositide-3-kinase signaling
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.763.3.7
– volume: 37
  start-page: 5678
  year: 2009
  ident: 10.1016/j.crphar.2021.100017_bib108
  article-title: Inhibition of ATR protein kinase activity by schisandrin B in DNA damage response
  publication-title: Nucleic Acids Res.
  doi: 10.1093/nar/gkp593
– volume: 281
  start-page: 1677
  year: 1998
  ident: 10.1016/j.crphar.2021.100017_bib25
  article-title: Activation of the ATM kinase by ionizing radiation and phosphorylation of p53
  publication-title: Science
  doi: 10.1126/science.281.5383.1677
– volume: 46
  start-page: 50
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib53
  article-title: Schisandrin B, attenuates cisplatin-induced oxidative stress, genotoxicity and neurotoxicity through modulating NF-kappaB pathway in mice
  publication-title: Free Radic. Res.
  doi: 10.3109/10715762.2011.638291
– volume: 11
  start-page: 4371
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib67
  article-title: Current status and future prospects of PARP inhibitor clinical trials in ovarian cancer
  publication-title: Canc. Manag. Res.
– volume: 164
  start-page: 273
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib119
  article-title: Inhibition of Wee1 sensitizes AML cells to ATR inhibitor VE-822-induced DNA damage and apoptosis
  publication-title: Biochem. Pharmacol.
  doi: 10.1016/j.bcp.2019.04.022
– volume: 76
  start-page: CT012
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib132
  article-title: Abstract CT012: phase 1 trial of first-in-class ATR inhibitor VX-970 in combination with cisplatin (Cis) in patients (pts) with advanced solid tumors (NCT02157792)
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2016-CT012
– volume: 5
  start-page: 689
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib73
  article-title: The concept of synthetic lethality in the context of anticancer therapy
  publication-title: Nat. Rev. Canc.
  doi: 10.1038/nrc1691
– volume: 19
  start-page: 169
  year: 2004
  ident: 10.1016/j.crphar.2021.100017_bib35
  article-title: Endogenous DNA damage in humans: a review of quantitative data
  publication-title: Mutagenesis
  doi: 10.1093/mutage/geh025
– volume: 73
  start-page: 3683
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib62
  article-title: ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-13-0110
– volume: 444
  start-page: 633
  year: 2006
  ident: 10.1016/j.crphar.2021.100017_bib14
  article-title: Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints
  publication-title: Nature
  doi: 10.1038/nature05268
– volume: 28
  start-page: 3067
  year: 2009
  ident: 10.1016/j.crphar.2021.100017_bib87
  article-title: Emerging common themes in regulation of PIKKs and PI3Ks
  publication-title: EMBO J.
  doi: 10.1038/emboj.2009.281
– volume: 13
  start-page: 738
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib11
  article-title: Mammalian G1- and S-phase checkpoints in response to DNA damage
  publication-title: Curr. Opin. Cell Biol.
  doi: 10.1016/S0955-0674(00)00280-5
– volume: 8
  start-page: 1307
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib139
  article-title: Inhibition of ATR downregulates PD-L1 and sensitizes tumor cells to T cell-mediated killing
  publication-title: Am. J. Cancer Res.
– volume: 129
  start-page: 1329
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib24
  article-title: Inhibiting Wee1 and ATR kinases produces tumor-selective synthetic lethality and suppresses metastasis
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI122622
– volume: 79
  start-page: 2933
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib32
  article-title: Inhibition of ataxia-telangiectasia mutated and RAD3-related (ATR) overcomes oxaliplatin resistance and promotes antitumor immunity in colorectal cancer
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-18-2807
– volume: 3
  start-page: 247
  year: 2003
  ident: 10.1016/j.crphar.2021.100017_bib136
  article-title: Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A
  publication-title: Canc. Cell
  doi: 10.1016/S1535-6108(03)00048-5
– volume: 277
  start-page: 1497
  year: 1997
  ident: 10.1016/j.crphar.2021.100017_bib126
  article-title: Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25
  publication-title: Science
  doi: 10.1126/science.277.5331.1497
– volume: 7
  start-page: 873
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib47
  article-title: Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer
  publication-title: Future Med. Chem.
  doi: 10.4155/fmc.15.33
– volume: 281
  start-page: 9346
  year: 2006
  ident: 10.1016/j.crphar.2021.100017_bib103
  article-title: Rapid activation of ATR by ionizing radiation requires ATM and Mre11
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M513265200
– ident: 10.1016/j.crphar.2021.100017_bib121
– volume: 178
  start-page: 193
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib29
  article-title: Biodegradable PEG-poly(ω-pentadecalactone-co-p-dioxanone) nanoparticles for enhanced and sustained drug delivery to treat brain tumors
  publication-title: Biomaterials
  doi: 10.1016/j.biomaterials.2018.06.024
– volume: 64
  start-page: 562
  year: 2006
  ident: 10.1016/j.crphar.2021.100017_bib137
  article-title: Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status
  publication-title: Int. J. Radiat. Oncol. Biol. Phys.
  doi: 10.1016/j.ijrobp.2005.09.031
– volume: 17
  start-page: 1670
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib151
  article-title: The ATR inhibitor AZD6738 synergizes with gemcitabine in vitro and in vivo to induce pancreatic ductal adenocarcinoma regression
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-18-0010
– volume: 16
  start-page: 566
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib101
  article-title: AZD6738, A novel oral inhibitor of ATR, induces synthetic lethality with ATM deficiency in gastric cancer cells
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-16-0378
– volume: 29
  start-page: viii519
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib117
  article-title: Phase I dose expansion data for M6620 (formerly VX-970), a first-in-class ATR inhibitor, combined with gemcitabine (Gem) in patients (pts) with advanced non-small cell lung cancer (NSCLC)
  publication-title: Ann. Oncol.
  doi: 10.1093/annonc/mdy292.059
– volume: 54
  start-page: 1473
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib90
  article-title: Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl) benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer
  publication-title: J. Med. Chem.
  doi: 10.1021/jm101520v
– volume: 62
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib80
  publication-title: J. Med. Chem.
  doi: 10.1021/acs.jmedchem.9b00426
– volume: 73
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib56
  article-title: The pre-clinical in vitro and in vivo activity of AZD6738: a potent and selective inhibitor of ATR kinase
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2013-3343
– volume: 42
  start-page: 30
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib155
  article-title: Breaking the DNA damage response to improve cervical cancer treatment
  publication-title: Canc. Treat Rev.
  doi: 10.1016/j.ctrv.2015.11.008
– volume: 100
  start-page: 57
  year: 2000
  ident: 10.1016/j.crphar.2021.100017_bib59
  article-title: The hallmarks of cancer
  publication-title: Cell
  doi: 10.1016/S0092-8674(00)81683-9
– volume: 294
  start-page: 1713
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib33
  article-title: ATR and ATRIP: partners in checkpoint signaling
  publication-title: Science
  doi: 10.1126/science.1065521
– volume: 56
  start-page: 2125
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib46
  article-title: Discovery of 4-{4-[(3R)-3-Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-y l}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity
  publication-title: J. Med. Chem.
  doi: 10.1021/jm301859s
– volume: 14
  start-page: PR14
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib161
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.TARG-15-PR14
– volume: 79
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib163
  article-title: Abstract 369: antitumor activity of M4344, a potent and selective ATR inhibitor, in monotherapy and combination therapy
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2019-369
– volume: 3
  start-page: 421
  year: 2003
  ident: 10.1016/j.crphar.2021.100017_bib12
  article-title: Chk1 and Chk2 kinases in checkpoint control and cancer
  publication-title: Canc. Cell
  doi: 10.1016/S1535-6108(03)00110-7
– volume: 278
  start-page: 21767
  year: 2003
  ident: 10.1016/j.crphar.2021.100017_bib158
  article-title: Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M300229200
– volume: 25
  start-page: 3392
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib37
  article-title: ATR inhibition potentiates the radiation-induced inflammatory tumor microenvironment
  publication-title: Clin. Canc. Res.
  doi: 10.1158/1078-0432.CCR-18-1821
– volume: 383
  start-page: 41
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib96
  article-title: Inhibition of ATR-dependent feedback activation of Chk1 sensitises cancer cells to Chk1 inhibitor monotherapy
  publication-title: Canc. Lett.
  doi: 10.1016/j.canlet.2016.09.024
– volume: 54
  start-page: 2320
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib28
  article-title: Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents
  publication-title: J. Med. Chem.
  doi: 10.1021/jm101488z
– volume: 18
  start-page: 721
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib145
  article-title: A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations
  publication-title: Nat. Struct. Mol. Biol.
  doi: 10.1038/nsmb.2076
– volume: 421
  start-page: 499
  year: 2003
  ident: 10.1016/j.crphar.2021.100017_bib6
  article-title: DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
  publication-title: Nature
  doi: 10.1038/nature01368
– ident: 10.1016/j.crphar.2021.100017_bib105
– volume: 73
  start-page: 39
  year: 2004
  ident: 10.1016/j.crphar.2021.100017_bib125
  article-title: Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints
  publication-title: Annu.l Rev. Biochem.
  doi: 10.1146/annurev.biochem.73.011303.073723
– volume: 10
  start-page: 213
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib4
  article-title: Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer
  publication-title: Mol. Oncol.
  doi: 10.1016/j.molonc.2015.09.009
– volume: 59
  start-page: 4375
  year: 1999
  ident: 10.1016/j.crphar.2021.100017_bib128
  article-title: Inhibition of ATM and ATR kinase activities by the radiosensitizing agent
  publication-title: Caffeine. Cancer Res
– volume: 9
  start-page: 616
  year: 2008
  ident: 10.1016/j.crphar.2021.100017_bib30
  article-title: ATR: an essential regulator of genome integrity
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/nrm2450
– volume: 41
  start-page: 1013
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib17
  article-title: The ATM/p53 pathway is commonly targeted for inactivation in squamous cell carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms
  publication-title: Oral Oncol.
  doi: 10.1016/j.oraloncology.2005.06.003
– volume: 22
  start-page: 4163
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib42
  article-title: Sulfonyl-morpholino-pyrimidines: SAR and development of a novel class of selective mTOR kinase inhibitor
  publication-title: Bioorg. Med. Chem. Lett
  doi: 10.1016/j.bmcl.2012.04.036
– volume: 13
  start-page: 1072
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib118
  article-title: The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy
  publication-title: Canc. Biol. Ther.
  doi: 10.4161/cbt.21093
– volume: 2
  start-page: 196
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib147
  article-title: Chromosomal stability and the DNA double-stranded break connection
  publication-title: Nat. Rev. Genet.
  doi: 10.1038/35056049
– volume: 9
  year: 2008
  ident: 10.1016/j.crphar.2021.100017_bib86
  article-title: Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer
  publication-title: Nat. Rev. Mol. Cell Biol.
– volume: 73
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib70
  article-title: Discovery of AZD6738, a potent and selective inhibitor with the potential to test the clinical efficacy of ATR kinase inhibition in cancer patients
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2013-2348
– volume: 11
  start-page: 220
  year: 2010
  ident: 10.1016/j.crphar.2021.100017_bib106
  article-title: Genomic instability--an evolving hallmark of cancer
  publication-title: Nat. Rev. Mol. Cell Biol.
  doi: 10.1038/nrm2858
– volume: 7
  start-page: 428
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib120
  article-title: Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR
  publication-title: Nat. Chem. Biol.
  doi: 10.1038/nchembio.573
– volume: 128
  start-page: 3926
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib149
  article-title: ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI96519
– volume: 36
  start-page: 713
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib39
  article-title: A phase II study of BEZ235 in patients with everolimus-resistant, advanced pancreatic neuroendocrine tumours
  publication-title: Anticancer Res.
– volume: 434
  start-page: 907
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib55
  article-title: Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
  publication-title: Nature
  doi: 10.1038/nature03485
– volume: 7
  start-page: 1851
  year: 2008
  ident: 10.1016/j.crphar.2021.100017_bib94
  article-title: Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-08-0017
– volume: 33
  start-page: 497
  year: 2003
  ident: 10.1016/j.crphar.2021.100017_bib110
  article-title: A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome
  publication-title: Nat. Genet.
  doi: 10.1038/ng1129
– volume: 18
  start-page: 762
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib104
  article-title: Inhibition of the replication stress response is a synthetic vulnerability in SCLC that acts synergistically in combination with cisplatin
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-18-0972
– volume: 60
  start-page: 139
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib27
  article-title: DNA damage response inhibitors: mechanisms and potential applications in cancer therapy
  publication-title: Canc. Treat Rev.
  doi: 10.1016/j.ctrv.2017.08.013
– volume: 121
  start-page: 232
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib88
  article-title: Preclinical testing of an Atr inhibitor demonstrates improved response to standard therapies for esophageal cancer
  publication-title: Radiother. Oncol.
  doi: 10.1016/j.radonc.2016.10.023
– volume: 58
  start-page: 4375
  year: 1998
  ident: 10.1016/j.crphar.2021.100017_bib127
  article-title: Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin
  publication-title: Canc. Res.
– volume: 52
  start-page: 17
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib18
  article-title: Olaparib for the treatment of ovarian cancer
  publication-title: Drugs Today
  doi: 10.1358/dot.2016.52.1.2440714
– volume: 6
  start-page: 44289
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib148
  article-title: The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo
  publication-title: Oncotarget
  doi: 10.18632/oncotarget.6247
– volume: 432
  start-page: 56
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib134
  article-title: The identification of the ATR inhibitor VE-822 as a therapeutic strategy for enhancing cisplatin chemosensitivity in esophageal squamous cell carcinoma
  publication-title: Canc. Lett.
  doi: 10.1016/j.canlet.2018.06.010
– volume: 149
  start-page: 124
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib153
  article-title: ATM and ATR as therapeutic targets in cancer
  publication-title: Pharmacol. Therapeut.
  doi: 10.1016/j.pharmthera.2014.12.001
– volume: 78
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib82
  article-title: Abstract CT026: phase I study of AZD6738, an inhibitor of ataxia telangiectasia Rad3-related (ATR), in combination with olaparib or durvalumab in patients (pts) with advanced solid cancers
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2018-CT026
– volume: 9
  start-page: 41
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib123
  article-title: Targeting the ATR-CHK1 Axis in cancer therapy
  publication-title: Cancers
  doi: 10.3390/cancers9050041
– volume: 361
  start-page: 123
  year: 2009
  ident: 10.1016/j.crphar.2021.100017_bib45
  article-title: Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers
  publication-title: N. Engl. J. Med.
  doi: 10.1056/NEJMoa0900212
– volume: 444
  start-page: 756
  year: 2006
  ident: 10.1016/j.crphar.2021.100017_bib7
  article-title: Glioma stem cells promote radioresistance by preferential activation of the DNA damage response
  publication-title: Nature
  doi: 10.1038/nature05236
– volume: 7
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib91
  article-title: Schisandrin B attenuates cancer invasion and metastasis via inhibiting epithelial-mesenchymal transition
  publication-title: PloS One
– volume: 4
  start-page: 32
  year: 2020
  ident: 10.1016/j.crphar.2021.100017_bib72
  article-title: RTB101 and immune function in the elderly: interpreting an unsuccessful clinical trial
  publication-title: Transl. Med. Aging
  doi: 10.1016/j.tma.2020.01.002
– volume: 12
  start-page: 323
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib156
  article-title: A phase ib study of the dual PI3K/mTOR inhibitor dactolisib (BEZ235) combined with everolimus in patients with advanced solid malignancies
  publication-title: Targeted Oncol.
  doi: 10.1007/s11523-017-0482-9
– volume: 12
  start-page: 149
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib69
  article-title: Olaparib recommendations for ovarian cancer patients
  publication-title: Future Oncol.
  doi: 10.2217/fon.15.257
– volume: 28
  start-page: 5736
  year: 2008
  ident: 10.1016/j.crphar.2021.100017_bib131
  article-title: A novel Tel1/ATM N-terminal motif, TAN, is essential for telomere length maintenance and a DNA damage response
  publication-title: Mol. Cell Biol.
  doi: 10.1128/MCB.00326-08
– volume: 68
  start-page: 1636
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib76
  article-title: Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival
  publication-title: Mol. Pharmacol.
  doi: 10.1124/mol.105.012716
– volume: 34
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib109
  article-title: Phase I trial of a first-in-class ATR inhibitor VX-970 as monotherapy (mono) or in combination (combo) with carboplatin (CP) incorporating pharmacodynamics (PD) studies
  publication-title: J. Clin. Oncol.
  doi: 10.1200/JCO.2016.34.15_suppl.2504
– volume: 23
  start-page: 882
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib160
  article-title: A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening
  publication-title: Cell stem cell
  doi: 10.1016/j.stem.2018.09.016
– volume: 13
  start-page: 3127
  year: 2004
  ident: 10.1016/j.crphar.2021.100017_bib3
  article-title: Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway
  publication-title: Hum. Mol. Genet.
  doi: 10.1093/hmg/ddh335
– volume: 25
  start-page: 9
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib95
  article-title: RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response
  publication-title: Cell Res.
  doi: 10.1038/cr.2014.147
– volume: 79
  start-page: 350
  year: 2019
  ident: 10.1016/j.crphar.2021.100017_bib8
  article-title: Abstract 350: investigating the mechanisms of cellular uptake and metabolism of ICT2588, an MT-MMP-activated prodrug
  publication-title: Canc. Res.
  doi: 10.1158/1538-7445.AM2019-350
– volume: 98
  start-page: 9092
  year: 2001
  ident: 10.1016/j.crphar.2021.100017_bib107
  article-title: ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation
  publication-title: Proc. Natl. Acad. Sci. Unit. States Am.
  doi: 10.1073/pnas.161281798
– volume: 122
  start-page: 241
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib130
  article-title: Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR
  publication-title: J. Clin. Invest.
  doi: 10.1172/JCI58928
– volume: 461
  start-page: 1071
  year: 2009
  ident: 10.1016/j.crphar.2021.100017_bib64
  article-title: The DNA-damage response in human biology and disease
  publication-title: Nature
  doi: 10.1038/nature08467
– volume: 32
  start-page: 308
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib49
  article-title: Anticancer therapy with checkpoint inhibitors: what, where and when?
  publication-title: Trends Pharmacol. Sci.
  doi: 10.1016/j.tips.2011.02.014
– volume: 107
  start-page: 291
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib115
  article-title: Targeting radiation-resistant hypoxic tumour cells through ATR inhibition
  publication-title: Br. J. Canc.
  doi: 10.1038/bjc.2012.265
– volume: 169
  start-page: 277
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib2
  article-title: Targeting ataxia telangiectasia-mutated- and Rad3-related kinase (ATR) in PTEN-deficient breast cancers for personalized therapy
  publication-title: Breast Canc. Res. Treat.
  doi: 10.1007/s10549-018-4683-4
– volume: 43
  start-page: 2797
  year: 2000
  ident: 10.1016/j.crphar.2021.100017_bib5
  article-title: Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles
  publication-title: J. Med. Chem.
  doi: 10.1021/jm990628o
– volume: 71
  start-page: 587
  year: 1992
  ident: 10.1016/j.crphar.2021.100017_bib78
  article-title: A mammalian-cell cycle checkpoint pathway utilizing P53 and Gadd45 is defective in ataxia-telangiectasia
  publication-title: Cell
  doi: 10.1016/0092-8674(92)90593-2
– volume: 10
  start-page: 8
  year: 2020
  ident: 10.1016/j.crphar.2021.100017_bib99
  article-title: ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion
  publication-title: Cell Biosci.
  doi: 10.1186/s13578-020-0376-x
– volume: 109
  start-page: 8230
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib77
  article-title: Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery
  publication-title: Proc. Natl. Acad. Sci. Unit. States Am.
  doi: 10.1073/pnas.1120508109
– volume: 6
  year: 2011
  ident: 10.1016/j.crphar.2021.100017_bib159
  article-title: Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo
  publication-title: PloS One
  doi: 10.1371/journal.pone.0028335
– volume: 502
  start-page: 333
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib74
  article-title: Mutational landscape and significance across 12 major cancer types
  publication-title: Nature
  doi: 10.1038/nature12634
– volume: 1
  start-page: 113
  year: 2007
  ident: 10.1016/j.crphar.2021.100017_bib124
  article-title: Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss
  publication-title: Cell stem cell
  doi: 10.1016/j.stem.2007.03.002
– volume: 280
  start-page: 15158
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib40
  article-title: DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATM
  publication-title: J. Biol. Chem.
  doi: 10.1074/jbc.M412065200
– volume: 69
  year: 2016
  ident: 10.1016/j.crphar.2021.100017_bib162
  article-title: 1LBA - phase I modular study of AZD6738, a novel oral, potent and selective ataxia telangiectasia Rad3-related (ATR) inhibitor in combination (combo) with carboplatin, olaparib or durvalumab in patients (pts) with advanced cancers
  publication-title: Eur. J. Canc.
  doi: 10.1016/S0959-8049(16)32607-7
– volume: 434
  start-page: 913
  year: 2005
  ident: 10.1016/j.crphar.2021.100017_bib23
  article-title: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
  publication-title: Nature
  doi: 10.1038/nature03443
– volume: 31
  start-page: 1661
  year: 2012
  ident: 10.1016/j.crphar.2021.100017_bib41
  article-title: Efficacy of CHK inhibitors as single agents in MYC-driven lymphoma cells
  publication-title: Oncogene
  doi: 10.1038/onc.2011.358
– volume: 147
  start-page: 695
  year: 2017
  ident: 10.1016/j.crphar.2021.100017_bib16
  article-title: PARP inhibitors: clinical utility and possibilities of overcoming resistance
  publication-title: Gynecol. Oncol.
  doi: 10.1016/j.ygyno.2017.10.003
– volume: 22
  start-page: 297
  year: 2008
  ident: 10.1016/j.crphar.2021.100017_bib144
  article-title: ATR signaling can drive cells into senescence in the absence of DNA breaks
  publication-title: Gene Dev.
  doi: 10.1101/gad.452308
– volume: 73
  start-page: 2574
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib92
  article-title: Characterization of Torin2, an ATP-competitive inhibitor of mTOR, ATM, and ATR
  publication-title: Canc. Res.
  doi: 10.1158/0008-5472.CAN-12-1702
– volume: 6
  start-page: 37
  year: 2015
  ident: 10.1016/j.crphar.2021.100017_bib9
  article-title: Structure-based drug design of novel potent and selective tetrahydropyrazolo[1,5-a]pyrazines as ATR inhibitors
  publication-title: ACS Med. Chem. Lett.
  doi: 10.1021/ml500353p
– volume: 17
  start-page: 2462
  year: 2018
  ident: 10.1016/j.crphar.2021.100017_bib146
  article-title: ATR inhibition is a promising radiosensitizing strategy for triple-negative breast cancer
  publication-title: Mol. Canc. Therapeut.
  doi: 10.1158/1535-7163.MCT-18-0470
– volume: 14
  start-page: 379
  year: 2013
  ident: 10.1016/j.crphar.2021.100017_bib157
  article-title: Chemotherapy induced DNA damage response Convergence of drugs and pathways
  publication-title: Canc. Biol. Ther.
  doi: 10.4161/cbt.23761
– volume: 12
  start-page: 440
  year: 2006
  ident: 10.1016/j.crphar.2021.100017_bib122
  article-title: DNA damage-induced cell death by apoptosis
  publication-title: Trends Mol. Med.
  doi: 10.1016/j.molmed.2006.07.007
– volume: 17
  start-page: 615
  year: 2003
  ident: 10.1016/j.crphar.2021.100017_bib21
  article-title: Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance
  publication-title: Genes Dev.
  doi: 10.1101/gad.1067403
– volume: 23
  start-page: 1895
  year: 2009
  ident: 10.1016/j.crphar.2021.100017_bib66
  article-title: The combined status of ATM and p53 link tumor development with therapeutic response
  publication-title: Gene Dev.
  doi: 10.1101/gad.1815309
SSID ssj0002794068
Score 2.4422162
SecondaryResourceType review_article
Snippet The DNA damage response (DDR) is now known to play an important role in both cancer development and its treatment. Targeting proteins such as ATR (Ataxia...
SourceID doaj
pubmedcentral
proquest
pubmed
crossref
elsevier
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 100017
SubjectTerms ATM
ATR
ATR inhibitors
Chemo- and radiosensitisers
DDR
Review
Title Progress towards a clinically-successful ATR inhibitor for cancer therapy
URI https://dx.doi.org/10.1016/j.crphar.2021.100017
https://www.ncbi.nlm.nih.gov/pubmed/34909652
https://www.proquest.com/docview/2610407668
https://pubmed.ncbi.nlm.nih.gov/PMC8663972
https://doaj.org/article/119315a7ae774e0fb0ba04253dc5fc6e
Volume 2
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1LbxMxELZQT1wQb8KjMhLqqRbetb22j4CoChIoQqnUm-WnmqraojwO-feM7d084JAL12Q3zux89nxez3yD0Iem63jQSZKYgiQ8hki0bxkQOeY9k0oHmeudf_zsLq_492txvdfqK-eEVXng-uA-NsAwGmGljUBUIk2OOpuBxoIXyXcxr74Q8_Y2U7flOE1DpCrt6ISmBHDZjHVzJbnLgxE2y4G2Tc4ToKVf2S4uFfn-g_D0L_38O4tyLyxdPEaPBj6JP1U7nqAHsX-KzqZVkHpzjme7-qrlOT7D051U9eYZ-jbN6Vmw2OFVSZ9dYovHWsm7DVmuSzvFtIYBZr_wvL-ZO1gBFhiYLvYZLwtcC7g2z9HVxdfZl0syNFcgHqahJNY2yQplW-okT1RpGmiC7Z5orE3ae8et5z5QLlliTUxeB6BOPHGZlBaJshfopL_v4yuEeRYF1JI6rxRnTLoO4iFPQkmrnQh8gtj4aI0flMdzA4w7M6aY3ZrqEJMdYqpDJohs7_pdlTeOXP85e217bdbNLh8AmsyAJnMMTRMkR5-bgYJUagE_NT8y_PsRIgZmaD52sX28Xy8N7FFhpZRdpyboZYXM9k8yrrP8TgvjHoDpwIrDb_r5TVEBV10-k21f_w-z36CH2ZT6auktOlkt1vEdkK2VOy3z6rS8BfsDSIcoMA
linkProvider Directory of Open Access Journals
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Progress+towards+a+clinically-successful+ATR+inhibitor+for+cancer+therapy&rft.jtitle=Current+research+in+pharmacology+and+drug+discovery&rft.au=Barnieh%2C+Francis+M.&rft.au=Loadman%2C+Paul+M.&rft.au=Falconer%2C+Robert+A.&rft.date=2021-01-01&rft.pub=Elsevier&rft.eissn=2590-2571&rft.volume=2&rft_id=info:doi/10.1016%2Fj.crphar.2021.100017&rft_id=info%3Apmid%2F34909652&rft.externalDocID=PMC8663972
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2590-2571&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2590-2571&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2590-2571&client=summon