Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9(8):616–627. https://doi.org/10.1038/nrm2450
Article CAS PubMed Central PubMed Google Scholar
Fokas E, Prevo R, Hammond EM, Brunner TB, McKenna WG, Muschel RJ (2014) Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat Rev 40(1):109–117. https://doi.org/10.1016/j.ctrv.2013.03.002
Article CAS PubMed Google Scholar
Zeman MK, Cimprich KA (2014) Causes and consequences of replication stress. Nat Cell Biol 16(1):2–9. https://doi.org/10.1038/ncb2897
Article CAS PubMed Central PubMed Google Scholar
Weber AM, Ryan AJ (2015) ATM and ATR as therapeutic targets in cancer. Pharmacol Ther 149:124–138. https://doi.org/10.1016/j.pharmthera.2014.12.001
Article CAS PubMed 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 Central PubMed Google Scholar
Brown EJ, Baltimore D (2000) ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev 14(4):397–402
Article CAS PubMed Central PubMed Google Scholar
Vendetti FP, Lau A, Schamus S, Conrads TP, O’Connor MJ, Bakkenist CJ (2015) 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. Oncotarget 6(42):44289–44305. https://doi.org/10.18632/oncotarget.6247
Article PubMed Central PubMed Google Scholar
Villaruz LC, Jones H, Dacic S, Abberbock S, Kurland BF, Stabile LP, Siegfried JM, Conrads TP, Smith NR, O’Connor MJ, Pierce AJ, Bakkenist CJ (2016) ATM protein is deficient in over 40% of lung adenocarcinomas. Oncotarget 7(36):57714–57725. https://doi.org/10.18632/oncotarget.9757
Article PubMed Central PubMed 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
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 Investig 128(9):3926–3940. https://doi.org/10.1172/JCI96519
Article PubMed Central PubMed Google Scholar
Wang C, Wang G, Feng X, Shepherd P, Zhang J, Tang M, Chen Z, Srivastava M, McLaughlin ME, Navone NM, Hart GT, Chen J (2019) Genome-wide CRISPR screens reveal synthetic lethality of RNASEH2 deficiency and ATR inhibition. Oncogene 38(14):2451–2463. https://doi.org/10.1038/s41388-018-0606-4
Article CAS PubMed Google Scholar
Hustedt N, Alvarez-Quilon A, McEwan A, Yuan JY, Cho T, Koob L, Hart T, Durocher D (2019) A consensus set of genetic vulnerabilities to ATR inhibition. Open Biol 9(9):190156. https://doi.org/10.1098/rsob.190156
Article CAS PubMed Central PubMed Google Scholar
Mohni KN, Thompson PS, Luzwick JW, Glick GG, Pendleton CS, Lehmann BD, Pietenpol JA, Cortez D (2015) A synthetic lethal screen identifies DNA repair pathways that sensitize cancer cells to combined ATR inhibition and cisplatin treatments. PLoS ONE 10(5):e0125482. https://doi.org/10.1371/journal.pone.0125482
Article CAS PubMed Central PubMed Google Scholar
Sugitani N, Vendetti FP, Cipriano AJ, Pandya P, Deppas JJ, Moiseeva TN, Schamus-Haynes S, Wang Y, Palmer D, Osmanbeyoglu HU, Bostwick A, Snyder NW, Gong YN, Aird KM, Delgoffe GM, Beumer JH, Bakkenist CJ (2022) Thymidine rescues ATR kinase inhibitor-induced deoxyuridine contamination in genomic DNA, cell death, and interferon-alpha/beta expression. Cell Rep 40(12):111371. https://doi.org/10.1016/j.celrep.2022.111371
Article CAS PubMed Central PubMed Google Scholar
Kim ST, Smith SA, Mortimer P, Loembe AB, Cho H, Kim KM, Smith C, Willis S, Irurzun-Arana I, Berges A, Hong JY, Park SH, Park JO, Park YS, Lim HY, Kang WK, Kozarewa I, Pierce AJ, Dean E, Lee J (2021) Phase I study of ceralasertib (AZD6738), a novel DNA damage repair agent, in combination with weekly paclitaxel in refractory cancer. Clin Cancer Res 27(17):4700–4709. https://doi.org/10.1158/1078-0432.CCR-21-0251
Article PubMed Central PubMed 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 Central PubMed Google Scholar
Shapiro GI, Wesolowski R, Devoe C, Lord S, Pollard J, Hendriks BS, Falk M, Diaz-Padilla I, Plummer R, Yap TA (2021) Phase 1 study of the ATR inhibitor berzosertib in combination with cisplatin in patients with advanced solid tumours. Br J Cancer 125(4):520–527. https://doi.org/10.1038/s41416-021-01406-w
Article CAS PubMed Central PubMed Google Scholar
Thomas A, Redon CE, Sciuto L, Padiernos E, Ji J, Lee MJ, Yuno A, Lee S, Zhang Y, Tran L, Yutzy W, Rajan A, Guha U, Chen H, Hassan R, Alewine CC, Szabo E, Bates SE, Kinders RJ, Steinberg SM, Doroshow JH, Aladjem MI, Trepel JB, Pommier Y (2018) Phase I study of ATR inhibitor M6620 in combination with topotecan in patients with advanced solid tumors. J Clin Oncol 36(16):1594–1602. https://doi.org/10.1200/JCO.2017.76.6915
Article CAS PubMed Google Scholar
Yap TA, Krebs MG, Postel-Vinay S, El-Khouiery A, Soria JC, Lopez J, Berges A, Cheung SYA, Irurzun-Arana I, Goldwin A, Felicetti B, Jones GN, Lau A, Frewer P, Pierce AJ, Clack G, Stephens C, Smith SA, Dean E, Hollingsworth SJ (2021) Ceralasertib (AZD6738), an oral ATR kinase inhibitor, in combination with carboplatin in patients with advanced solid tumors: a phase I study. Clin Cancer Res 27(19):5213–5224. https://doi.org/10.1158/1078-0432.CCR-21-1032
Article CAS PubMed Central PubMed Google Scholar
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 Off J Am Soc Clin Oncol 38(27):3195–3204. https://doi.org/10.1200/JCO.19.02404
Stockton S, Shyr C, Cecchini M, Aljumaily R, Halfdanarson TR, Sonbol MB, Whisenant J, Ivy SP, LoRusso P, Das S, Gore S, Berlin J, Beumer JH, Heumann TR A phase I study of ATR inhibitor BAY1895344 (elimusertib) plus topotecan (ETCTN 10402): Results of dose escalation. In: 2024 ASCO Annual Meeting, Chicago, 2024. vol suppl 16. p 3076. https://doi.org/10.1200/JCO.2024.42.16_suppl.3076
Heumann TR, Stockton S, Cecchini M, Aljumaily R, Shyr C, Whisenant J, Starr JS, Dayyani F, Baranda JC, Trikalinos N, Ivy SP, LoRusso P, Das S, Gore S, Beumer JH, Berlin J A phase I study of irinotecan combined with BAY1895344 (ATR inhibitor) in advanced solid tumors: Results of ETCTN 10402 dose escalation. In: 2024 ASCO Annual Meeting, Chicago, 2024. vol suppl 16. p 3077. https://doi.org/10.1200/JCO.2024.42.16_suppl.3077
Foote KM, Nissink JWM, McGuire T, Turner P, Guichard S, Yates JWT, Lau A, Blades K, Heathcote D, Odedra R, Wilkinson G, Wilson Z, Wood CM, Jewsbury PJ (2018) Discovery and characterization of AZD6738, a potent inhibitor of ataxia telangiectasia mutated and Rad3 related (ATR) kinase with application as an anticancer agent. J Med Chem 61(22):9889–9907. https://doi.org/10.1021/acs.jmedchem.8b01187
Article CAS PubMed Google Scholar
Hall AB, Newsome D, Wang Y, Boucher DM, Eustace B, Gu Y, Hare B, Johnson MA, Milton S, Murphy CE, Takemoto D, Tolman C, Wood M, Charlton P, Charrier JD, Furey B, Golec J, Reaper PM, Pollard JR (2014) Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970. Oncotarget 5(14):5674–5685. https://doi.org/10.18632/oncotarget.2158
Article PubMed Central PubMed Google Scholar
Wengner AM, Siemeister G, Lucking U, Lefranc J, Wortmann L, Lienau P, Bader B, Bomer U, Moosmayer D, Eberspacher U, Golfier S, Schatz CA, Baumgart SJ, Haendler B, Lejeune P, Schlicker A, von Nussbaum F, Brands M, Ziegelbauer K, Mumberg D (2020) The novel ATR inhibitor BAY 1895344 is efficacious as monotherapy and combined with DNA damage-inducing or repair-compromising therapies in preclinical cancer models. Mol Cancer Ther 19(1):26–38. https://doi.org/10.1158/1535-7163.MCT-19-0019
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