{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:58:47Z","timestamp":1792277927224,"version":"4.4.0"},"reference-count":41,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","gynecologiconcology-online.net","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Gynecologic Oncology"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.ygyno.2022.09.019","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T07:36:48Z","timestamp":1664523408000},"page":"213-225","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":69,"title":["A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer"],"prefix":"10.1016","volume":"167","author":[{"given":"Panagiotis A.","family":"Konstantinopoulos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-min","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowan","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Yun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignace","family":"Vergote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Credille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne R.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"McNeely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing Aimee","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee Bence","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Shapira-Frommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.ygyno.2022.09.019_bb0005","doi-asserted-by":"crossref","first-page":"952","DOI":"10.3390\/ijms20040952","article-title":"High-grade serous ovarian cancer: basic sciences, clinical and therapeutic standpoints","volume":"20","author":"Lisio","year":"2019","journal-title":"Int J Mol Sci."},{"issue":"7","key":"10.1016\/j.ygyno.2022.09.019_bb0010","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/13543784.2021.1939305","article-title":"Advances in the treatment of platinum resistant epithelial ovarian cancer: an update on standard and experimental therapies","volume":"30","author":"Leung","year":"2021","journal-title":"Expert Opin Investig Drugs."},{"issue":"13","key":"10.1016\/j.ygyno.2022.09.019_bb0015","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1200\/JCO.2013.51.4489","article-title":"Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial","volume":"32","author":"Pujade-Lauraine","year":"2014","journal-title":"J Clin Oncol."},{"issue":"3","key":"10.1016\/j.ygyno.2022.09.019_bb0020","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ygyno.2017.10.003","article-title":"PARP inhibitors: Clinical utility and possibilities of overcoming resistance","volume":"147","author":"Bitler","year":"2017","journal-title":"Gynecologic Oncology."},{"issue":"8","key":"10.1016\/j.ygyno.2022.09.019_bb0025","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1080\/13543784.2020.1783238","article-title":"Prexasertib: an investigational checkpoint kinase inhibitor for the treatment of high-grade serous ovarian cancer","volume":"29","author":"Evangelisti","year":"2020","journal-title":"Expert Opin Investig Drugs."},{"issue":"11","key":"10.1016\/j.ygyno.2022.09.019_bb0030","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1158\/2159-8290.CD-15-0714","article-title":"Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer","volume":"5","author":"Konstantinopoulos","year":"2015","journal-title":"Cancer Discov."},{"issue":"2","key":"10.1016\/j.ygyno.2022.09.019_bb0035","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrc.2015.21","article-title":"BRCAness revisited","volume":"16","author":"Lord","year":"2016","journal-title":"Nat Rev Cancer."},{"issue":"48","key":"10.1016\/j.ygyno.2022.09.019_bb0040","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1314302110","article-title":"Synthetic lethality between CCNE1 amplification and loss of BRCA1","volume":"110","author":"Etemadmoghadam","year":"2013","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"32","key":"10.1016\/j.ygyno.2022.09.019_bb0045","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1038\/onc.2012.387","article-title":"Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress","volume":"32","author":"Jones","year":"2013","journal-title":"Oncogene."},{"issue":"2","key":"10.1016\/j.ygyno.2022.09.019_bb0050","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ygyno.2020.01.038","article-title":"CCNE1 and BRD4 co-amplification in high-grade serous ovarian cancer is associated with poor clinical outcomes","volume":"157","author":"Petersen","year":"2020","journal-title":"Gynecol Oncol."},{"issue":"2","key":"10.1016\/j.ygyno.2022.09.019_bb0055","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1158\/2159-8290.CD-20-0818","article-title":"Genetically defined syngeneic mouse models of ovarian cancer as tools for the discovery of combination immunotherapy","volume":"11","author":"Iyer","year":"2021","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ygyno.2022.09.019_bb0060","series-title":"AACR-NCI-EORTC International Conference: Molecular Targets and Cancer.","article-title":"Abstract A108: LY2606368, a second generation Chk1 inhibitor, inhibits growth of ovarian carcinoma xenografts either as monotherapy or in combination with standard-of-care agents","author":"McNeely Samuel","year":"2011"},{"issue":"20","key":"10.1016\/j.ygyno.2022.09.019_bb0065","doi-asserted-by":"crossref","first-page":"6127","DOI":"10.1158\/1078-0432.CCR-19-0448","article-title":"The CHK1 inhibitor prexasertib exhibits monotherapy activity in high-grade serous ovarian cancer models and sensitizes to PARP inhibition","volume":"25","author":"Parmar","year":"2019","journal-title":"Clin Cancer Res."},{"issue":"11","key":"10.1016\/j.ygyno.2022.09.019_bb0070","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1158\/2159-8290.CD-18-0474","article-title":"Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids","volume":"8","author":"Hill","year":"2018","journal-title":"Cancer Discov."},{"issue":"2","key":"10.1016\/j.ygyno.2022.09.019_bb0075","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1470-2045(18)30009-3","article-title":"Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study","volume":"19","author":"Lee","year":"2018","journal-title":"The Lancet Oncol."},{"issue":"4","key":"10.1016\/j.ygyno.2022.09.019_bb0080","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/carcin\/bgx002","article-title":"DNA-damage response in hematopoietic stem cells: an evolutionary trade-off between blood regeneration and leukemia suppression","volume":"38","author":"Biechonski","year":"2017","journal-title":"Carcinogenesis."},{"issue":"2","key":"10.1016\/j.ygyno.2022.09.019_bb0085","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/jat.1177","article-title":"Peripheral white blood cell toxicity induced by broad spectrum cyclin-dependent kinase inhibitors","volume":"27","author":"Jessen","year":"2007","journal-title":"J Appl Toxicol."},{"issue":"20","key":"10.1016\/j.ygyno.2022.09.019_bb0090","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"issue":"6","key":"10.1016\/j.ygyno.2022.09.019_bb0095","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/00000421-198212000-00014","article-title":"Toxicity and response criteria of the Eastern Cooperative Oncology Group","volume":"5","author":"Oken","year":"1982","journal-title":"Am J Clin Oncol."},{"issue":"2","key":"10.1016\/j.ygyno.2022.09.019_bb0100","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur J Cancer."},{"key":"10.1016\/j.ygyno.2022.09.019_bb0105","author":"U.S. Department of health and human services NIoH"},{"issue":"1","key":"10.1016\/j.ygyno.2022.09.019_bb0110","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S1470-2045(11)70318-7","article-title":"EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study","volume":"13","author":"Pirker","year":"2012","journal-title":"Lancet Oncol."},{"issue":"3","key":"10.1016\/j.ygyno.2022.09.019_bb0115","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.ygyno.2014.02.038","article-title":"\u201cPlatinum resistant\u201d ovarian cancer: what is it, who to treat and how to measure benefit?","volume":"133","author":"Davis","year":"2014","journal-title":"Gynecol Oncol."},{"issue":"6","key":"10.1016\/j.ygyno.2022.09.019_bb0120","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1200\/JCO.2007.13.6606","article-title":"Phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in progressive or recurrent ovarian cancer","volume":"26","author":"Ferrandina","year":"2008","journal-title":"J Clin Oncol."},{"issue":"14","key":"10.1016\/j.ygyno.2022.09.019_bb0125","doi-asserted-by":"crossref","first-page":"3312","DOI":"10.1200\/JCO.2001.19.14.3312","article-title":"Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan","volume":"19","author":"Gordon","year":"2001","journal-title":"J Clin Oncol."},{"issue":"3","key":"10.1016\/j.ygyno.2022.09.019_bb0130","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ygyno.2005.10.036","article-title":"Phase II trial of weekly paclitaxel (80 mg\/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study","volume":"101","author":"Oncology Group","year":"2006","journal-title":"Gynecol Oncol."},{"issue":"19","key":"10.1016\/j.ygyno.2022.09.019_bb0135","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1200\/JCO.2006.09.6735","article-title":"Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer","volume":"25","author":"Mutch","year":"2007","journal-title":"J Clin Oncol."},{"issue":"21","key":"10.1016\/j.ygyno.2022.09.019_bb0140","first-page":"00089","article-title":"A phase II trial of prexasertib (LY2606368) in patients with extensive-stage small-cell lung cancer","volume":"S1525-7304","author":"Byers","year":"2021","journal-title":"Clin Lung Cancer."},{"issue":"14","key":"10.1016\/j.ygyno.2022.09.019_bb0145","doi-asserted-by":"crossref","first-page":"3263","DOI":"10.1158\/1078-0432.CCR-17-3347","article-title":"Evaluation of prexasertib, a checkpoint kinase 1 inhibitor, in a phase Ib study of patients with squamous cell carcinoma","volume":"24","author":"Hong","year":"2018","journal-title":"Clin Cancer Res."},{"issue":"15_suppl","key":"10.1016\/j.ygyno.2022.09.019_bb0150","doi-asserted-by":"crossref","first-page":"6038","DOI":"10.1200\/JCO.2020.38.15_suppl.6038","article-title":"Prexasertib, a cell cycle checkpoint kinase 1 inhibitor, in BRCA mutant recurrent high-grade serous ovarian cancer (HGSOC): A proof-of-concept single arm phase II study","volume":"38","author":"Lampert","year":"2020","journal-title":"J Clin Oncol."},{"issue":"7353","key":"10.1016\/j.ygyno.2022.09.019_bb0155","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Cancer Genome Atlas Research N. Integrated genomic analyses of ovarian carcinoma","volume":"474","year":"2011","journal-title":"Nature."},{"issue":"4","key":"10.1016\/j.ygyno.2022.09.019_bb0160","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1158\/0008-5472.CAN-13-2247","article-title":"Cyclin E1 deregulation occurs early in secretory cell transformation to promote formation of fallopian tube-derived high-grade serous ovarian cancers","volume":"74","author":"Karst","year":"2014","journal-title":"Cancer Res."},{"issue":"3","key":"10.1016\/j.ygyno.2022.09.019_bb0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.molcel.2020.10.008","article-title":"CHK1 inhibitor blocks phosphorylation of FAM122A and promotes replication stress","volume":"80","author":"Li","year":"2020","journal-title":"Mol Cell."},{"issue":"33","key":"10.1016\/j.ygyno.2022.09.019_bb0170","doi-asserted-by":"crossref","first-page":"5520","DOI":"10.1038\/s41388-020-1383-4","article-title":"Resistance to the CHK1 inhibitor prexasertib involves functionally distinct CHK1 activities in BRCA wild-type ovarian cancer","volume":"39","author":"Nair","year":"2020","journal-title":"Oncogene."},{"key":"10.1016\/j.ygyno.2022.09.019_bb0175","doi-asserted-by":"crossref","DOI":"10.1038\/s41571-021-00532-x","article-title":"Understanding and overcoming resistance to PARP inhibitors in cancer therapy","author":"Dias","year":"2021","journal-title":"Nat Rev Clin Oncol."},{"issue":"5","key":"10.1016\/j.ygyno.2022.09.019_bb0180","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1158\/2159-8290.CD-18-1020","article-title":"Targeting DNA damage response promotes antitumor immunity through STING-mediated T-cell activation in small cell lung cancer","volume":"9","author":"Sen","year":"2019","journal-title":"Cancer Discov."},{"issue":"67","key":"10.1016\/j.ygyno.2022.09.019_bb0185","doi-asserted-by":"crossref","first-page":"111026","DOI":"10.18632\/oncotarget.22195","article-title":"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","volume":"8","author":"Brill","year":"2017","journal-title":"Oncotarget."},{"issue":"3","key":"10.1016\/j.ygyno.2022.09.019_bb0190","doi-asserted-by":"crossref","first-page":"819","DOI":"10.4143\/crt.2020.1013","article-title":"Enhanced efficacy of combined therapy with checkpoint kinase 1 inhibitor and rucaparib via regulation of rad51 expression in BRCA wild-type epithelial ovarian cancer cells","volume":"53","author":"Cho","year":"2021","journal-title":"Cancer Res Treat."},{"issue":"14","key":"10.1016\/j.ygyno.2022.09.019_bb0195","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1158\/0008-5472.CAN-16-3409","article-title":"CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib","volume":"77","author":"Sen","year":"2017","journal-title":"Cancer Res."},{"issue":"10","key":"10.1016\/j.ygyno.2022.09.019_bb0200","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1007\/s00262-021-02910-x","article-title":"Immune modulating activity of the CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 in patients with high-grade serous ovarian cancer and other solid tumors","volume":"70","author":"Do","year":"2021","journal-title":"Cancer Immunol Immunother."},{"issue":"17","key":"10.1016\/j.ygyno.2022.09.019_bb0205","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1158\/1078-0432.CCR-21-1279","article-title":"Phase 1 Combination Study of the CHK1 Inhibitor Prexasertib and the PARP Inhibitor Olaparib in High-grade Serous Ovarian Cancer and Other Solid Tumors","volume":"27","author":"Do","year":"2021","journal-title":"Clin Cancer Res."}],"container-title":["Gynecologic Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S009082582201839X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S009082582201839X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T04:04:07Z","timestamp":1758773047000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S009082582201839X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":41,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["S009082582201839X"],"URL":"https:\/\/doi.org\/10.1016\/j.ygyno.2022.09.019","relation":{},"ISSN":["0090-8258"],"issn-type":[{"value":"0090-8258","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer","name":"articletitle","label":"Article Title"},{"value":"Gynecologic Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ygyno.2022.09.019","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}