{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:42:48Z","timestamp":1794008568569,"version":"4.8.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["JP25K18687"],"award-info":[{"award-number":["JP25K18687"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"a Grant-in-Aid for Young Scientists of Showa Pharmaceutical University","id":[{"id":"https:\/\/ror.org\/053e8a708","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>PARP inhibitors have shown limited efficacy in pancreatic cancer, partly due to the low prevalence of BRCA mutations, which restricts their clinical use. Because DNA damage checkpoint kinases play critical roles in managing replication stress and DNA damage responses, we investigated whether ATR, Chk1, and WEE1 inhibitors enhance the antitumor activity of olaparib in pancreatic cancer cells, including gemcitabine-resistant clones, and compared these effects with standard chemotherapeutic agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cell viability was evaluated in pancreatic cancer cell lines treated with olaparib in combination with various agents using an MTT assay. Apoptosis was assessed by annexin V and propidium iodide double staining followed by flow cytometry. The combinatorial effects were further examined using an in vivo mouse xenograft model. In addition, the effects of combination therapy were evaluated in gemcitabine-resistant cell clones (BxG140 and BxG400) overexpressing ribonucleotide reductase M1 (RRM1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Co-treatment with olaparib and DNA damage checkpoint inhibitors led to a greater reduction in cell viability than combinations with conventional chemotherapeutics. Notably, olaparib combined with the Chk1 inhibitor prexasertib elicited strong synergistic cytotoxicity in BRCA1\/2 wild-type MIA PaCa-2 and BxPC-3 cells, whereas the effect was minimal in BRCA2-deficient Capan-1 cells. Compared with monotherapy, combination therapy markedly enhanced apoptosis and suppressed tumor growth in xenograft models. In gemcitabine-resistant clones, olaparib plus prexasertib downregulated RRM1 expression and restored drug sensitivity through enhanced apoptotic cell death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Combined PARP and Chk1 inhibition exerts potent antitumor activity both in vitro and in vivo in pancreatic cancer models, including BRCA-proficient tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12672-026-05581-1","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:35:07Z","timestamp":1784039707000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chk1 inhibition emerges as the most effective partner for PARP inhibition in BRCA-proficient pancreatic cancer"],"prefix":"10.1007","volume":"17","author":[{"given":"Yoshihito","family":"Morimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Musha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Inano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Hirohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"5581_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2022;74:229\u201363. https:\/\/doi.org\/10.3322\/caac.21834.","journal-title":"CA Cancer J Clin"},{"key":"5581_CR2","doi-asserted-by":"publisher","first-page":"19","DOI":"10.21037\/cco-21-87","volume":"11","author":"T Okusaka","year":"2022","unstructured":"Okusaka T. Treatment for postoperative recurrence of pancreatic cancer: a narrative review. Chin Clin Oncol. 2022;11:19. https:\/\/doi.org\/10.21037\/cco-21-87.","journal-title":"Chin Clin Oncol"},{"key":"5581_CR3","doi-asserted-by":"publisher","first-page":"4846","DOI":"10.3748\/wjg.v24.i43.4846","volume":"24","author":"A McGuigan","year":"2018","unstructured":"McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: a review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018;24:4846\u201361. https:\/\/doi.org\/10.3748\/wjg.v24.i43.4846.","journal-title":"World J Gastroenterol"},{"key":"5581_CR4","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","volume":"369","author":"DD Von Hoff","year":"2013","unstructured":"Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691\u2013703. https:\/\/doi.org\/10.1056\/NEJMoa1304369.","journal-title":"N Engl J Med"},{"key":"5581_CR5","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","volume":"364","author":"T Conroy","year":"2011","unstructured":"Conroy T, Desseigne F, Ychou M, Bouch\u00e9 O, Guimbaud R, B\u00e9couarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817\u201325. https:\/\/doi.org\/10.1056\/NEJMoa1011923.","journal-title":"N Engl J Med"},{"key":"5581_CR6","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1007\/s40265-020-01336-6","volume":"80","author":"JE Frampton","year":"2020","unstructured":"Frampton JE. Liposomal irinotecan: a review in metastatic pancreatic adenocarcinoma. Drugs. 2020;80:1007\u201318. https:\/\/doi.org\/10.1007\/s40265-020-01336-6.","journal-title":"Drugs"},{"key":"5581_CR7","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.1200\/JCO.21.01604","volume":"40","author":"HL Kindler","year":"2022","unstructured":"Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Overall survival results from the POLO trial: a phase III study of active maintenance olaparib versus placebo for germline BRCA-mutated metastatic pancreatic cancer. J Clin Oncol. 2022;40:3929\u201339. https:\/\/doi.org\/10.1200\/JCO.21.01604.","journal-title":"J Clin Oncol"},{"key":"5581_CR8","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1097\/CAD.0b013e328350e8c7","volume":"23","author":"Y Morimoto","year":"2012","unstructured":"Morimoto Y, Takeuchi O, Takizawa A, Yoneyama H, Asanuma F, Suzuki Y, et al. Effect of a combination of S-1 and gemcitabine on cell cycle regulation in pancreatic cancer cell lines. Anticancer Drugs. 2012;23:505\u201314. https:\/\/doi.org\/10.1097\/CAD.0b013e328350e8c7.","journal-title":"Anticancer Drugs"},{"key":"5581_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-025-01488-8","volume":"17","author":"K Nesic","year":"2025","unstructured":"Nesic K, Parker P, Swisher EM, Krais JJ. DNA repair and the contribution to chemotherapy resistance. Genome Med. 2025;17:62. https:\/\/doi.org\/10.1186\/s13073-025-01488-8.","journal-title":"Genome Med"},{"key":"5581_CR10","doi-asserted-by":"publisher","first-page":"689","DOI":"10.3892\/or.2019.7421","volume":"43","author":"Y Morimoto","year":"2020","unstructured":"Morimoto Y, Takada K, Takeuchi O, Takagi A, Watanabe K, Hirohara M, et al. Prexasertib increases the sensitivity of pancreatic cancer cells to gemcitabine and S-1. Oncol Rep. 2020;43:689\u201399. https:\/\/doi.org\/10.3892\/or.2019.7421.","journal-title":"Oncol Rep"},{"key":"5581_CR11","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1007\/s00280-024-04716-x","volume":"94","author":"Y Morimoto","year":"2024","unstructured":"Morimoto Y, Takada K, Nakano A, Takeuchi O, Watanabe K, Hirohara M, et al. Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells. Cancer Chemother Pharmacol. 2024;94:763\u201374. https:\/\/doi.org\/10.1007\/s00280-024-04716-x.","journal-title":"Cancer Chemother Pharmacol"},{"key":"5581_CR12","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/s41416-024-02745-0","volume":"131","author":"HL Smith","year":"2024","unstructured":"Smith HL, Willmore E, Prendergast L, Curtin NJ. ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors. Br J Cancer. 2024;131:905\u201317. https:\/\/doi.org\/10.1038\/s41416-024-02745-0.","journal-title":"Br J Cancer"},{"key":"5581_CR13","doi-asserted-by":"publisher","first-page":"2800","DOI":"10.1158\/1078-0432.CCR-22-2444","volume":"29","author":"SL Wethington","year":"2023","unstructured":"Wethington SL, Shah PD, Martin L, Tanyi JL, Latif N, Morgan M, et al. Combination ATR (ceralasertib) and PARP (olaparib) inhibitor (CAPRI) trial in acquired PARP inhibitor-resistant homologous recombination-deficient ovarian cancer. Clin Cancer Res. 2023;29:2800\u20137. https:\/\/doi.org\/10.1158\/1078-0432.CCR-22-2444.","journal-title":"Clin Cancer Res"},{"key":"5581_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27031152","volume":"27","author":"M Kciuk","year":"2026","unstructured":"Kciuk M, Wanke K, Marciniak B, Ko\u0142at D, Aleksandrowicz M, Mujwar S, et al. Targeting ATR-CHK1 and ATM-CHK2 axes in pancreatic cancer\u2014a comprehensive review of literature. Int J Mol Sci. 2026;27:1152. https:\/\/doi.org\/10.3390\/ijms27031152.","journal-title":"Int J Mol Sci"},{"key":"5581_CR15","doi-asserted-by":"publisher","first-page":"541","DOI":"10.4143\/crt.2021.473","volume":"54","author":"HR Seo","year":"2022","unstructured":"Seo HR, Nam AR, Bang JH, Oh KS, Kim JM, Yoon J, et al. Inhibition of WEE1 potentiates sensitivity to PARP inhibitor in biliary tract cancer. Cancer Res Treat. 2022;54:541\u201353. https:\/\/doi.org\/10.4143\/crt.2021.473.","journal-title":"Cancer Res Treat"},{"key":"5581_CR16","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1097\/CAD.0000000000000165","volume":"26","author":"H Yoneyama","year":"2015","unstructured":"Yoneyama H, Takizawa-Hashimoto A, Takeuchi O, Watanabe Y, Atsuda K, Asanuma F, et al. Acquired resistance to gemcitabine and cross-resistance in human pancreatic cancer clones. Anticancer Drugs. 2015;26:90\u2013100. https:\/\/doi.org\/10.1097\/CAD.0000000000000165.","journal-title":"Anticancer Drugs"},{"key":"5581_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111892","volume":"147","author":"X Wu","year":"2021","unstructured":"Wu X, Li Q, Zhang F, Wang L, Wang J, Fan J, et al. Novel poly(ADP-ribose) polymerases inhibitor DHC-1 exhibits in vitro and in vivo anticancer activity on BRCA-deficient pancreatic cancer cells. Food Chem Toxicol. 2021;147:111892. https:\/\/doi.org\/10.1016\/j.fct.2020.111892.","journal-title":"Food Chem Toxicol"},{"key":"5581_CR18","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70:440\u20136. https:\/\/doi.org\/10.1158\/0008-5472.CAN-09-1947.","journal-title":"Cancer Res"},{"key":"5581_CR19","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1158\/0008-5472.CAN-21-2997","volume":"82","author":"Z Wilson","year":"2022","unstructured":"Wilson Z, Odedra R, Wallez Y, Wijnhoven PWG, Hughes AM, Gerrard J, et al. ATR inhibitor AZD6738 (ceralasertib) exerts antitumor activity as a monotherapy and in combination with chemotherapy and the PARP inhibitor olaparib. Cancer Res. 2022;82:1140\u201352. https:\/\/doi.org\/10.1158\/0008-5472.CAN-21-2997.","journal-title":"Cancer Res"},{"key":"5581_CR20","doi-asserted-by":"publisher","first-page":"3870","DOI":"10.1158\/0008-5472.CAN-16-3409","volume":"77","author":"T Sen","year":"2017","unstructured":"Sen T, Tong P, Stewart CA, Cristea S, Valliani A, Shames DS, et al. CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib. Cancer Res. 2017;77:3870\u201384. https:\/\/doi.org\/10.1158\/0008-5472.CAN-16-3409.","journal-title":"Cancer Res"},{"key":"5581_CR21","doi-asserted-by":"publisher","first-page":"764","DOI":"10.3892\/ijo.2018.4662","volume":"54","author":"K Suzuki","year":"2019","unstructured":"Suzuki K, Takeuchi O, Suzuki Y, Kitagawa Y. Mechanisms of metformin\u2019s anti-tumor activity against gemcitabine-resistant pancreatic adenocarcinoma. Int J Oncol. 2019;54:764\u201372. https:\/\/doi.org\/10.3892\/ijo.2018.4662.","journal-title":"Int J Oncol"},{"key":"5581_CR22","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1111\/tpj.15567","volume":"109","author":"JA Pedroza-Garcia","year":"2022","unstructured":"Pedroza-Garcia JA, Xiang Y, De Veylder L. Cell cycle checkpoint control in response to DNA damage by environmental stresses. Plant J. 2022;109:490\u2013507. https:\/\/doi.org\/10.1111\/tpj.15567.","journal-title":"Plant J"},{"key":"5581_CR23","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/B978-0-12-380888-2.00003-0","volume":"108","author":"J Smith","year":"2010","unstructured":"Smith J, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010;108:73\u2013112. https:\/\/doi.org\/10.1016\/B978-0-12-380888-2.00003-0.","journal-title":"Adv Cancer Res"},{"key":"5581_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0433-9","volume":"35","author":"R Visconti","year":"2016","unstructured":"Visconti R, Della Monica R, Grieco D. Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword. J Exp Clin Cancer Res. 2016;35:153. https:\/\/doi.org\/10.1186\/s13046-016-0433-9.","journal-title":"J Exp Clin Cancer Res"},{"key":"5581_CR25","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.radonc.2017.09.043","volume":"126","author":"Z Qiu","year":"2018","unstructured":"Qiu Z, Oleinick NL, Zhang J. ATR\/CHK1 inhibitors and cancer therapy. Radiother Oncol. 2018;126:450\u201364. https:\/\/doi.org\/10.1016\/j.radonc.2017.09.043.","journal-title":"Radiother Oncol"},{"key":"5581_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01360-x","volume":"15","author":"S Li","year":"2022","unstructured":"Li S, Wang L, Wang Y, Zhang C, Hong Z, Han Z. The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment. J Hematol Oncol. 2022;15:147. https:\/\/doi.org\/10.1186\/s13045-022-01360-x.","journal-title":"J Hematol Oncol"},{"key":"5581_CR27","doi-asserted-by":"publisher","first-page":"111026","DOI":"10.18632\/oncotarget.22195","volume":"8","author":"E Brill","year":"2017","unstructured":"Brill E, Yokoyama T, Nair J, Yu M, Ahn YR, Lee JM. Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget. 2017;8:111026\u201340. https:\/\/doi.org\/10.18632\/oncotarget.22195.","journal-title":"Oncotarget"},{"key":"5581_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12040878","volume":"12","author":"HL Smith","year":"2020","unstructured":"Smith HL, Prendergast L, Curtin NJ. Exploring the synergy between PARP and CHK1 inhibition in matched BRCA2 mutant and corrected cells. Cancers (Basel). 2020;12:878. https:\/\/doi.org\/10.3390\/cancers12040878.","journal-title":"Cancers (Basel)"},{"key":"5581_CR29","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17127-2","volume":"11","author":"H Kim","year":"2020","unstructured":"Kim H, Xu H, George E, Hallberg D, Kumar S, Jagannathan V, et al. Combining PARP with ATR inhibition overcomes PARP inhibitor and platinum resistance in ovarian cancer models. Nat Commun. 2020;11:3726. https:\/\/doi.org\/10.1038\/s41467-020-17127-2.","journal-title":"Nat Commun"},{"key":"5581_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.109978","volume":"27","author":"H Xu","year":"2024","unstructured":"Xu H, Gitto SB, Ho GY, Medvedev S, Shield-Artin K, Kim H, et al. CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer. iScience. 2024;27:109978. https:\/\/doi.org\/10.1016\/j.isci.2024.109978.","journal-title":"iScience"},{"key":"5581_CR31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s00280-019-03950-y","volume":"85","author":"G Angius","year":"2020","unstructured":"Angius G, Tomao S, Stati V, Vici P, Bianco V, Tomao F. Prexasertib, a checkpoint kinase inhibitor: from preclinical data to clinical development. Cancer Chemother Pharmacol. 2020;85:9\u201320. https:\/\/doi.org\/10.1007\/s00280-019-03950-y.","journal-title":"Cancer Chemother Pharmacol"},{"key":"5581_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82780-6","volume":"11","author":"S Moens","year":"2021","unstructured":"Moens S, Zhao P, Baietti MF, Marinelli O, Van Haver D, Impens F, et al. The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers. Sci Rep. 2021;11:3176. https:\/\/doi.org\/10.1038\/s41598-021-82780-6.","journal-title":"Sci Rep"},{"key":"5581_CR33","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.cllc.2021.04.005","volume":"22","author":"LA Byers","year":"2021","unstructured":"Byers LA, Navarro A, Schaefer E, Johnson M, \u00d6zg\u00fcro\u011flu M, Han JY, et al. A phase II trial of Prexasertib (LY2606368) in patients with extensive\u2011stage small\u2011cell lung cancer. Clin Lung Cancer. 2021;22:531\u201340. https:\/\/doi.org\/10.1016\/j.cllc.2021.04.005.","journal-title":"Clin Lung Cancer"},{"key":"5581_CR34","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1634\/theoncologist.2020-0491","volume":"25","author":"ME Gatti\u2011Mays","year":"2020","unstructured":"Gatti\u2011Mays ME, Karzai FH, Soltani SN, Zimmer A, Green JE, Lee MJ, et al. A phase II single arm pilot study of the CHK1 inhibitor Prexasertib (LY2606368) in BRCA wild\u2011type, advanced triple\u2011negative breast cancer. Oncologist. 2020;25:1013-e1824. https:\/\/doi.org\/10.1634\/theoncologist.2020-0491.","journal-title":"Oncologist"},{"key":"5581_CR35","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.ygyno.2022.09.019","volume":"167","author":"PA Konstantinopoulos","year":"2022","unstructured":"Konstantinopoulos PA, Lee JM, Gao B, Miller R, Lee JY, Colombo N, et al. A phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer. Gynecol Oncol. 2022;167:213\u201325. https:\/\/doi.org\/10.1016\/j.ygyno.2022.09.019.","journal-title":"Gynecol Oncol"},{"key":"5581_CR36","doi-asserted-by":"publisher","first-page":"4869","DOI":"10.1038\/s41388-020-1328-y","volume":"39","author":"RL Lloyd","year":"2020","unstructured":"Lloyd RL, Wijnhoven PWG, Ramos\u2011Montoya A, Wilson Z, Illuzzi G, Falenta K, et al. Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM\u2011deficient cancer cells. Oncogene. 2020;39:4869\u201383. https:\/\/doi.org\/10.1038\/s41388-020-1328-y.","journal-title":"Oncogene"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-026-05581-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05581-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-026-05581-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:03:00Z","timestamp":1791468180000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-026-05581-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5581"],"URL":"https:\/\/doi.org\/10.1007\/s12672-026-05581-1","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"assertion":[{"value":"19 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were reviewed and approved by the Animal Experiment Committee of Showa Pharmaceutical University on July 16, 2024 (approval no. 2024-13) and were conducted in accordance with the institutional regulations and the university\u2019s animal experiment manual. Consent to participate was not applicable as this study did not involve human participants.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"1414"}}