{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:59:38Z","timestamp":1791377978232,"version":"4.3.2"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","thegreenjournal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Radiotherapy and Oncology"],"published-print":{"date-parts":[[2023,8]]},"DOI":"10.1016\/j.radonc.2023.109669","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T11:13:40Z","timestamp":1681211620000},"page":"109669","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer"],"prefix":"10.1016","volume":"185","author":[{"given":"Lucjan","family":"Wyrwicz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0039-5041","authenticated-orcid":false,"given":"Marcia","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-0239","authenticated-orcid":false,"given":"John","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8481-6581","authenticated-orcid":false,"given":"Theodore","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Lautermilch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Formenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6742-222X","authenticated-orcid":false,"given":"Robert","family":"Glynne-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.radonc.2023.109669_b0005","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ejso.2013.10.029","article-title":"EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology expert\u2019s review","volume":"40","author":"Tudyka","year":"2014","journal-title":"Eur J Surg Oncol"},{"key":"10.1016\/j.radonc.2023.109669_b0010","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1007\/s00330-017-5026-2","article-title":"Magnetic resonance imaging for clinical management of rectal cancer: Updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting","volume":"28","author":"Beets-Tan","year":"2018","journal-title":"Eur Radiol"},{"key":"10.1016\/j.radonc.2023.109669_b0015","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1200\/JCO.2011.39.7901","article-title":"Neoadjuvant treatment response as an early response indicator for patients with rectal cancer","volume":"30","author":"Park","year":"2012","journal-title":"J Clin Oncol"},{"key":"10.1016\/j.radonc.2023.109669_b0020","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"10.1016\/j.radonc.2023.109669_b0025","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41577-021-00534-x","article-title":"The inflammatory pathogenesis of colorectal cancer","volume":"21","author":"Schmitt","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.radonc.2023.109669_b0030","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1056\/NEJMoa051424","article-title":"Effector memory T cells, early metastasis, and survival in colorectal cancer","volume":"353","author":"Pag\u00e8s","year":"2005","journal-title":"N Engl J Med"},{"key":"10.1016\/j.radonc.2023.109669_b0035","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1158\/1078-0432.CCR-13-2830","article-title":"Prognostic and predictive values of the immunoscore in patients with rectal cancer","volume":"20","author":"Anitei","year":"2014","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.radonc.2023.109669_b0040","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3857\/roj.2017.00269","article-title":"Effect of leukocyte alteration on treatment outcomes following preoperative chemoradiotherapy in patients with rectal cancer","volume":"35","author":"Kim","year":"2017","journal-title":"Radiat Oncol J"},{"key":"10.1016\/j.radonc.2023.109669_b0045","doi-asserted-by":"crossref","first-page":"438","DOI":"10.4103\/jcrt.jcrt_1807_21","article-title":"Systemic inflammation-based predictors of pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients","volume":"18","author":"Xu","year":"2022","journal-title":"J Cancer Res Ther"},{"key":"10.1016\/j.radonc.2023.109669_b0050","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1158\/1078-0432.CCR-20-0337","article-title":"A diagnostic biopsy-adapted immunoscore predicts response to neoadjuvant treatment and selects patients with rectal cancer eligible for a watch-and-wait strategy","volume":"26","author":"El Sissy","year":"2020","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.radonc.2023.109669_b0055","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s00423-023-02786-8","article-title":"Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis","volume":"408","author":"Portale","year":"2023","journal-title":"Langenbecks Arch Surg"},{"key":"10.1016\/j.radonc.2023.109669_b0060","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-3-0348-0837-8_2","article-title":"The role of inflammation in colon cancer","volume":"816","author":"Janakiram","year":"2014","journal-title":"Adv Exp Med Biol"},{"key":"10.1016\/j.radonc.2023.109669_b0065","doi-asserted-by":"crossref","first-page":"e58891","DOI":"10.1371\/journal.pone.0058891","article-title":"Prognostic significance of COX-2 immunohistochemical expression in colorectal cancer: a meta-analysis of the literature","volume":"8","author":"Peng","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.radonc.2023.109669_b0070","doi-asserted-by":"crossref","first-page":"5239","DOI":"10.1111\/bph.13331","article-title":"Prostaglandin E2 and the EP receptors in malignancy: possible therapeutic targets?","volume":"172","author":"O'Callaghan","year":"2015","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.radonc.2023.109669_b0075","doi-asserted-by":"crossref","first-page":"e000222","DOI":"10.1136\/jitc-2019-000222","article-title":"First-in-human phase I study of immunomodulatory E7046, an antagonist of PGE2-receptor E-type 4 (EP4), in patients with advanced cancers","volume":"8","author":"Hong","year":"2020","journal-title":"J Immunother Cancer"},{"key":"10.1016\/j.radonc.2023.109669_b0080","doi-asserted-by":"crossref","first-page":"S128","DOI":"10.1016\/j.ijrobp.2016.06.312","article-title":"Combination of a novel ep4 antagonist e7046 and radiation therapy promotes anti-tumor immune response and tumor rejection in preclinical tumor models","volume":"96","author":"Bao","year":"2016","journal-title":"Int J Radiation Oncol Biol Phys"},{"key":"10.1016\/j.radonc.2023.109669_b0085","doi-asserted-by":"crossref","first-page":"e1338239","DOI":"10.1080\/2162402X.2017.1338239","article-title":"EP4 Antagonism by E7046 diminishes Myeloid immunosuppression and synergizes with Treg-reducing IL-2-Diphtheria toxin fusion protein in restoring anti-tumor immunity","volume":"6","author":"Albu","year":"2017","journal-title":"Oncoimmunology"},{"key":"10.1016\/j.radonc.2023.109669_b0090","doi-asserted-by":"crossref","first-page":"837","DOI":"10.4049\/immunohorizons.2000089","article-title":"Enhanced immunotherapeutic efficacy of anti\u2013PD-L1 antibody in combination with an EP4 antagonist.\u201c","volume":"4","author":"Sakiki","year":"2020","journal-title":"immunohorizons"},{"key":"10.1016\/j.radonc.2023.109669_b0095","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00262-018-2200-6","article-title":"Interactions among myeloid regulatory cells in cancer","volume":"68","author":"Umansky","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"10.1016\/j.radonc.2023.109669_b0100","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.3389\/fimmu.2020.01680","article-title":"The new era of cancer immunotherapy: Targeting myeloid-derived suppressor cells to overcome immune evasion","volume":"11","author":"De Cicco","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.radonc.2023.109669_b0105","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.3389\/fimmu.2018.02759","article-title":"Combination strategies to optimize efficacy of dendritic cell-based immunotherapy","volume":"9","author":"van Gulijk","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.radonc.2023.109669_b0110","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/bjs.5506","article-title":"Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer","volume":"93","author":"Bujko","year":"2006","journal-title":"Br J Surg"},{"key":"10.1016\/j.radonc.2023.109669_b0115","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1093\/annonc\/mdw062","article-title":"Long-course oxaliplatin-based preoperative chemoradiation versus 5 \u00d7 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study","volume":"27","author":"Bujko","year":"2016","journal-title":"Ann Oncol"},{"key":"10.1016\/j.radonc.2023.109669_b0120","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s10151-005-0226-1","article-title":"The circumferential resection margin in rectal carcinoma surgery","volume":"9","author":"Hermanek","year":"2005","journal-title":"Tech Coloproctol"},{"key":"10.1016\/j.radonc.2023.109669_b0125","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1097\/DCR.0000000000000667","article-title":"Magnetic resonance tumor regression grade and residual mucosal abnormality as predictors for pathological complete response in rectal cancer post neoadjuvant chemoradiotherapy","volume":"59","author":"Bhoday","year":"2016","journal-title":"Dis Colon Rectum"},{"key":"10.1016\/j.radonc.2023.109669_b0130","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0959-8049(02)00741-4","article-title":"Quality of life during radiotherapy for rectal cancer","volume":"39","author":"Guren","year":"2003","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.radonc.2023.109669_b0135","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1002\/bjs.8702","article-title":"Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer","volume":"99","author":"Martin","year":"2012","journal-title":"Br J Surg"},{"key":"10.1016\/j.radonc.2023.109669_b0140","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S1470-2045(12)70187-0","volume":"13","author":"R\u00f6del","year":"2012","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.radonc.2023.109669_b0145","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S1470-2045(15)00159-X","volume":"16","author":"R\u00f6del","year":"2015","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.radonc.2023.109669_b0150","doi-asserted-by":"crossref","unstructured":"Bahadoer R, Dijkstra E. Patterns of locoregional failure in patients treated within the RAPIDO trial\/The influence of total neoadjuvant treatment on the development and location of distant metastases in patients with locally advanced rectal in the RAPIDO trial. EJSO 2022;48: e29-e43 (ESSO40-0649r).","DOI":"10.1016\/j.ejso.2021.12.439"},{"key":"10.1016\/j.radonc.2023.109669_b0155","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1470-2045(21)00079-6","volume":"22","author":"Conroy","year":"2021","journal-title":"Lancet Oncol"}],"container-title":["Radiotherapy and Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814023002074?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814023002074?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:26:06Z","timestamp":1759123566000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167814023002074"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":31,"alternative-id":["S0167814023002074"],"URL":"https:\/\/doi.org\/10.1016\/j.radonc.2023.109669","relation":{},"ISSN":["0167-8140"],"issn-type":[{"value":"0167-8140","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer","name":"articletitle","label":"Article Title"},{"value":"Radiotherapy and Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.radonc.2023.109669","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"109669"}}