Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078. https://doi.org/10.1038/nature08467

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ciccia A, Elledge SJ (2010) The DNA damage response: making it safe to play with knives. Mol Cell 40(2):179–204. https://doi.org/10.1016/j.molcel.2010.09.019

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liao H, Ji F, Helleday T, Ying S (2018) Mechanisms for stalled replication fork stabilization: new targets for synthetic lethality strategies in cancer treatments. EMBO Rep. https://doi.org/10.15252/embr.201846263

Article  PubMed  PubMed Central  Google Scholar 

Smith HL, Southgate H, Tweddle DA, Curtin NJ (2020) DNA damage checkpoint kinases in cancer. Expert Rev Mol Med. https://doi.org/10.1017/erm.2020.3

Article  PubMed  Google Scholar 

Hoffmann I, Draetta G, Karsenti E (1994) Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J 13(18):4302–4310. https://doi.org/10.1002/j.1460-2075.1994.tb06750.x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bartek J, Lukas J (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3(5):421–429. https://doi.org/10.1016/s1535-6108(03)00110-7

Article  CAS  PubMed  Google Scholar 

Vendetti FP, Pandya P, Clump DA, Schamus-Haynes S, Tavakoli M, diMayorca M, Islam NM, Chang J, Delgoffe GM, Beumer JH, Bakkenist CJ (2023) The schedule of ATR inhibitor AZD6738 can potentiate or abolish antitumor immune responses to radiotherapy. JCI Insight. https://doi.org/10.1172/jci.insight.165615

Article  PubMed  PubMed Central  Google Scholar 

Vendetti FP, Karukonda P, Clump DA, Teo T, Lalonde R, Nugent K, Ballew M, Kiesel BF, Beumer JH, Sarkar SN, Conrads TP, O’Connor MJ, Ferris RL, Tran PT, Delgoffe GM, Bakkenist CJ (2018) ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation. J Clin Invest 128(9):3926–3940. https://doi.org/10.1172/JCI96519

Article  PubMed  PubMed Central  Google Scholar 

Sheng H, Huang Y, Xiao Y, Zhu Z, Shen M, Zhou P, Guo Z, Wang J, Wang H, Dai W, Zhang W, Sun J, Cao C (2020) ATR inhibitor AZD6738 enhances the antitumor activity of radiotherapy and immune checkpoint inhibitors by potentiating the tumor immune microenvironment in hepatocellular carcinoma. J Immunother Cancer. https://doi.org/10.1136/jitc-2019-000340

Article  PubMed  PubMed Central  Google Scholar 

Reaper PM, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR (2011) Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol 7(7):428–430. https://doi.org/10.1038/nchembio.573

Article  CAS  PubMed  Google Scholar 

Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W, Muschel RJ, Brunner TB (2012) Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis 3(12):e441. https://doi.org/10.1038/cddis.2012.181

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilson Z, Odedra R, Wallez Y, Wijnhoven PWG, Hughes AM, Gerrard J, Jones GN, Bargh-Dawson H, Brown E, Young LA, O’Connor MJ, Lau A (2022) ATR inhibitor AZD6738 (ceralasertib) exerts antitumor activity as a monotherapy and in combination with chemotherapy and the PARP inhibitor olaparib. Cancer Res 82(6):1140–1152. https://doi.org/10.1158/0008-5472.CAN-21-2997

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kiesel BF, Guo J, Parise RA, Venkataramanan R, Clump DA, Bakkenist CJ, Beumer JH (2022) Dose-dependent bioavailability and tissue distribution of the ATR inhibitor AZD6738 (ceralasertib) in mice. Cancer Chemother Pharmacol 89(2):231–242. https://doi.org/10.1007/s00280-021-04388-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kiesel BF, Deppas JJ, Guo J, Parise RA, Clump DA, Bakkenist CJ, Beumer JH (2022) Dose-dependent bioavailability, absorption-rate limited elimination, and tissue distribution of the ATR inhibitor BAY-1895344 (elimusertib) in mice. Cancer Chemother Pharmacol 89(6):795–807. https://doi.org/10.1007/s00280-022-04436-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kiesel BF, Scemama J, Parise RA, Villaruz L, Iffland A, Doyle A, Ivy P, Chu E, Bakkenist CJ, Beumer JH (2017) LC-MS/MS assay for the quantitation of the ATR kinase inhibitor VX-970 in human plasma. J Pharm Biomed Anal 146:244–250. https://doi.org/10.1016/j.jpba.2017.08.037

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bailer AJ (1988) Testing for the equality of area under the curves when using destructive measurement techniques. J Pharmacokinet Biopharm 16(3):303–309. https://doi.org/10.1007/BF01062139

Article  CAS  PubMed  Google Scholar 

Hummel J, McKendrick S, Brindley C, French R (2009) Exploratory assessment of dose proportionality: review of current approaches and proposal for a practical criterion. Pharm Stat 8(1):38–49. https://doi.org/10.1002/pst.326

Article  PubMed  Google Scholar 

Zaias J, Mineau M, Cray C, Yoon D, Altman NH (2009) Reference values for serum proteins of common laboratory rodent strains. J Am Assoc Lab Anim Sci 48(4):387–390

CAS  PubMed  PubMed Central  Google Scholar 

D’Argenio DZS, A; Wang, X, (2009) ADAPT 5 user’s guide: Pharmacokinetic/Pharmacodynamic systems analysis software. Biomedical Simulations Resource, Los Angeles

Google Scholar 

U.S. Department of Health and Human Services Food and Drug Administration (2018) Guidance for Industry-Bioanalytical Method Validation. U.S.Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research (CDER); Center for Veterinary Medicine (CVM)

Yap TA, O’Carrigan B, Penney MS, Lim JS, Brown JS, de Miguel Luken MJ, Tunariu N, Perez-Lopez R, Rodrigues DN, Riisnaes R, Figueiredo I, Carreira S, Hare B, McDermott K, Khalique S, Williamson CT, Natrajan R, Pettitt SJ, Lord CJ, Banerji U, Pollard J, Lopez J, de Bono JS (2020) Phase I trial of first-in-class ATR inhibitor M6620 (VX-970) as monotherapy or in combination with carboplatin in patients with advanced solid tumors. J Clin Oncol 38(27):3195–3204. https://doi.org/10.1200/JCO.19.02404

Article  CAS  PubMed  PubMed Central  Google Scholar 

Talele S, Zhang W, Burgenske DM, Kim M, Mohammad AS, Dragojevic S, Gupta SK, Bindra RS, Sarkaria JN, Elmquist WF (2021) Brain distribution of berzosertib: an ataxia telangiectasia and Rad3-related protein inhibitor for the treatment of glioblastoma. J Pharmacol Exp Ther 379(3):343–357. https://doi.org/10.1124/jpet.121.000845

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pal SK, Frankel PH, Mortazavi A, Milowsky M, Vaishampayan U, Parikh M, Lyou Y, Weng P, Parikh R, Teply B, Dreicer R, Emamekhoo H, Michaelson D, Hoimes C, Zhang T, Srinivas S, Kim WY, Cui Y, Newman E, Lara PN Jr (2021) Effect of cisplatin and gemcitabine with or without berzosertib in patients with advanced urothelial carcinoma: a phase 2 randomized clinical trial. JAMA Oncol 7(10):1536–1543. https://doi.org/10.1001/jamaoncol.2021.3441

Article  PubMed  Google Scholar 

Konstantinopoulos PA, Cheng SC, Wahner Hendrickson AE, Penson RT, Schumer ST, Doyle LA, Lee EK, Kohn EC, Duska LR, Crispens MA, Olawaiye AB, Winer IS, Barroilhet LM, Fu S, McHale MT, Schilder RJ, Farkkila A, Chowdhury D, Curtis J, Quinn RS, Bowes B, D’Andrea AD, Shapiro GI, Matulonis UA (2020) Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol 21(7):957–968. https://doi.org/10.1016/S1470-2045(20)30180-7

Article  CAS  PubMed  PubMed Central  Google Scholar 

Middleton MR, Dean E, Evans TRJ, Shapiro GI, Pollard J, Hendriks BS, Falk M, Diaz-Padilla I, Plummer R (2021) Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine +/- cisplatin in patients with advanced solid tumours. Br J Cancer 125(4):510–519. https://doi.org/10.1038/s41416-021-01405-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Telli ML, Tolaney SM, Shapiro GI, Middleton M, Lord SR, Arkenau HT, Tutt A, Abramson V, Dean E, Haddad TC, Wesolowski R, Ferrer-Playan J, Goddemeier T, Grombacher T, Dong J, Fleuranceau-Morel P, Diaz-Padilla I, Plummer R (2022) Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer. NPJ Breast Cancer 8(1):45. https://doi.org/10.1038/s41523-022-00406-0