{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T19:34:05Z","timestamp":1770320045903,"version":"3.49.0"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013348","name":"Innosuisse - Schweizerische Agentur f\u00fcr Innovationsf\u00f6rderung","doi-asserted-by":"publisher","award":["50865.1 IP-LS\/2150007631"],"award-info":[{"award-number":["50865.1 IP-LS\/2150007631"]}],"id":[{"id":"10.13039\/501100013348","id-type":"DOI","asserted-by":"publisher"}]}],"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":[[2026,2]]},"DOI":"10.1016\/j.radonc.2025.111331","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T17:18:33Z","timestamp":1765473513000},"page":"111331","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["The combined treatment with TOP-V122, a dual-acting NO-releasing PDE-5 inhibitor, and ionizing irradiation as a novel therapeutical strategy for colorectal carcinoma"],"prefix":"10.1016","volume":"215","author":[{"given":"Alba","family":"Sanchez-Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8406-1431","authenticated-orcid":false,"given":"Hermann","family":"Tenor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-6865","authenticated-orcid":false,"given":"Claire","family":"Beckers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal","family":"Pauli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzana","family":"Garajova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enni","family":"Markkanen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5297-8879","authenticated-orcid":false,"given":"Irene","family":"Vetrugno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lazaros","family":"Vasilikos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tobias","family":"Braun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esra Lone-","family":"Kapaklikaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshita","family":"Bhide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reto","family":"Naef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-9015","authenticated-orcid":false,"given":"Martin","family":"Pruschy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.radonc.2025.111331_b0005","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1470-2045(24)00600-4","article-title":"Colorectal cancer incidence trends in younger versus older adults: an analysis of population-based cancer registry data","volume":"26","author":"Sung","year":"2025","journal-title":"Lancet Oncol"},{"key":"10.1016\/j.radonc.2025.111331_b0010","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/jnci\/djab127","article-title":"Early-onset colorectal cancer: the mystery remains","volume":"113","author":"Eng","year":"2021","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.radonc.2025.111331_b0015","volume":"13","author":"Marcellinaro","year":"2023","journal-title":"Clin Med"},{"key":"10.1016\/j.radonc.2025.111331_b0020","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000446486","article-title":"Radiotherapy for colorectal cancer: current standards and future perspectives","volume":"32","author":"Hafner","year":"2016","journal-title":"Visc Med"},{"key":"10.1016\/j.radonc.2025.111331_b0025","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/jcb.30361","article-title":"Mechanisms of radioresistance and the underlying signaling pathways in colorectal cancer cells","volume":"124","author":"Tessmann","year":"2023","journal-title":"J Cell Biochem"},{"key":"10.1016\/j.radonc.2025.111331_b0030","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41575-019-0247-2","article-title":"Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers","volume":"17","author":"Buckley","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.radonc.2025.111331_b0035","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.semcancer.2023.11.006","article-title":"Tumor hypoxia and radiotherapy: a major driver of resistance even for novel radiotherapy modalities","volume":"98","author":"Beckers","year":"2024","journal-title":"Semin Cancer Biol"},{"key":"10.1016\/j.radonc.2025.111331_b0040","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1002\/bjs.10993","article-title":"Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer","volume":"105","author":"Clifford","year":"2018","journal-title":"Br J Surg"},{"key":"10.1016\/j.radonc.2025.111331_b0045","doi-asserted-by":"crossref","DOI":"10.3390\/nano12010169","article-title":"Molecular pathogenesis of colorectal cancer with an emphasis on recent advances in biomarkers, as well as nanotechnology-based diagnostic and therapeutic approaches","volume":"12","author":"Al-Joufi","year":"2022","journal-title":"Nanomaterials (Basel)"},{"key":"10.1016\/j.radonc.2025.111331_b0050","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.gie.2008.09.004","article-title":"The pathogenesis of colorectal cancer","volume":"68","author":"Axon","year":"2008","journal-title":"Foreword Gastrointest Endosc"},{"key":"10.1016\/j.radonc.2025.111331_b0055","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/MOG.0b013e328332b850","article-title":"Recent insights into the pathogenesis of colorectal cancer","volume":"26","author":"Goel","year":"2010","journal-title":"Curr Opin Gastroenterol"},{"key":"10.1016\/j.radonc.2025.111331_b0060","doi-asserted-by":"crossref","first-page":"131","DOI":"10.5217\/ir.2023.00115","article-title":"Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration","volume":"22","author":"Oh","year":"2024","journal-title":"Intest Res"},{"key":"10.1016\/j.radonc.2025.111331_b0065","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.2025.111331_b0070","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1124\/jpet.121.001075","article-title":"Inhibition of colon cancer cell growth by phosphodiesterase inhibitors is independent of cGMP signaling","volume":"381","author":"Hou","year":"2022","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.radonc.2025.111331_b0075","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.lfs.2019.05.043","article-title":"Therapeutic opportunities in colon cancer: focus on phosphodiesterase inhibitors","volume":"230","author":"Mehta","year":"2019","journal-title":"Life Sci"},{"key":"10.1016\/j.radonc.2025.111331_b0080","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3389\/fonc.2018.00299","article-title":"The guanylate cyclase C-cGMP signaling axis opposes intestinal epithelial injury and neoplasia","volume":"8","author":"Rappaport","year":"2018","journal-title":"Front Oncol"},{"key":"10.1016\/j.radonc.2025.111331_b0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2023.108337","article-title":"Heterogeneity of cGMP signalling in tumour cells and the tumour microenvironment: challenges and chances for cancer pharmacology and therapeutics","volume":"242","author":"Stehle","year":"2023","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.radonc.2025.111331_b0090","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1007\/s00384-021-04022-5","article-title":"Phosphodiesterase type 5 inhibitors use and risk of colorectal cancer: a systematic review and meta-analysis","volume":"36","author":"Bhagavathula","year":"2021","journal-title":"Int J Colorectal Dis"},{"key":"10.1016\/j.radonc.2025.111331_b0095","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1111\/codi.16724","article-title":"The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis","volume":"25","author":"Cullinane","year":"2023","journal-title":"Colorectal Dis"},{"key":"10.1016\/j.radonc.2025.111331_b0100","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1053\/j.gastro.2019.05.012","article-title":"Use of phosphodiesterase 5 inhibitors is associated with lower risk of colorectal cancer in men with benign colorectal neoplasms","volume":"157","author":"Huang","year":"2019","journal-title":"Gastroenterology"},{"key":"10.1016\/j.radonc.2025.111331_b0105","doi-asserted-by":"crossref","DOI":"10.14309\/ctg.0000000000000173","article-title":"The association between phosphodiesterase-5 inhibitors and colorectal cancer in a national cohort of patients","volume":"11","author":"Sutton","year":"2020","journal-title":"Clin Transl Gastroenterol"},{"key":"10.1016\/j.radonc.2025.111331_b0110","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1586\/17512433.2013.827406","article-title":"Translating colorectal cancer prevention through the guanylyl cyclase C signaling axis","volume":"6","author":"Blomain","year":"2013","journal-title":"Expert Rev Clin Pharmacol"},{"key":"10.1016\/j.radonc.2025.111331_b0115","doi-asserted-by":"crossref","first-page":"457","DOI":"10.2217\/pme-2022-0026","article-title":"Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer","volume":"19","author":"Caspi","year":"2022","journal-title":"Per Med"},{"key":"10.1016\/j.radonc.2025.111331_b0120","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1158\/1078-0432.CCR-09-0265","article-title":"Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti\u2013CTLA-4 antibody","volume":"15","author":"Dewan","year":"2009","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.radonc.2025.111331_b0125","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1080\/17512433.2020.1826304","article-title":"An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer","volume":"13","author":"Rappaport","year":"2020","journal-title":"Expert Rev Clin Pharmacol"},{"key":"10.1016\/j.radonc.2025.111331_b0130","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1136\/ard-2024-226430","article-title":"EULAR recommendations for the treatment of systemic sclerosis: 2023 update","volume":"84","author":"Del Galdo","year":"2025","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.radonc.2025.111331_b0135","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1158\/1940-6207.CAPR-17-0015","article-title":"Sildenafil suppresses inflammation-driven colorectal cancer in mice","volume":"10","author":"Islam","year":"2017","journal-title":"Cancer Prev Res (Phila)"},{"key":"10.1016\/j.radonc.2025.111331_b0140","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/cas.12148","article-title":"Early tumor shrinkage in metastatic colorectal cancer: retrospective analysis from an irinotecan-based randomized first-line trial","volume":"104","author":"Giessen","year":"2013","journal-title":"Cancer Sci"},{"key":"10.1016\/j.radonc.2025.111331_b0145","doi-asserted-by":"crossref","first-page":"814","DOI":"10.2533\/chimia.2020.814","article-title":"TOP-N53: a clinical drug candidate for the treatment of non-healing wounds","volume":"74","author":"Naef","year":"2020","journal-title":"Chimia (Aarau)"},{"key":"10.1016\/j.radonc.2025.111331_b0150","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jid.2020.05.111","article-title":"A Dual-acting nitric oxide donor and phosphodiesterase 5 inhibitor promotes wound healing in normal mice and mice with diabetes","volume":"141","author":"Ben-Yehuda Greenwald","year":"2021","journal-title":"J Invest Dermatol"},{"key":"10.1016\/j.radonc.2025.111331_b0155","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1038\/s41467-020-17028-4","article-title":"Phosphodiesterase-5 inhibitors use and risk for mortality and metastases among male patients with colorectal cancer","volume":"11","author":"Huang","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.radonc.2025.111331_b0160","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.sxmr.2015.10.004","article-title":"The role of PDE5 inhibitors and the NO\/cGMP pathway in cancer","volume":"4","author":"Peak","year":"2016","journal-title":"Sex Med Rev"},{"key":"10.1016\/j.radonc.2025.111331_b0165","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s42003-022-03244-9","article-title":"Author correction: PDGF regulates guanylate cyclase expression and cGMP signaling in vascular smooth muscle","volume":"5","author":"Hildebrand","year":"2022","journal-title":"Commun Biol"},{"key":"10.1016\/j.radonc.2025.111331_b0170","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13008-024-00116-y","article-title":"Cancer radioresistance is characterized by a differential lipid droplet content along the cell cycle","volume":"19","author":"Pagliari","year":"2024","journal-title":"Cell Div"},{"key":"10.1016\/j.radonc.2025.111331_b0175","doi-asserted-by":"crossref","first-page":"5858","DOI":"10.1074\/jbc.273.10.5858","article-title":"DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139","volume":"273","author":"Rogakou","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1016\/j.radonc.2025.111331_b0180","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24065252","article-title":"Canonical Wnt pathway is involved in chemoresistance and cell cycle arrest induction in colon cancer cell line spheroids","volume":"24","author":"Moreno-Londono","year":"2023","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.radonc.2025.111331_b0185","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3390\/cancers15051620","article-title":"Cancer-associated fibroblasts exposed to high-dose ionizing radiation promote M2 polarization of macrophages, which induce radiosensitivity in cervical cancer","volume":"15","author":"Sheng","year":"2023","journal-title":"Cancers"},{"key":"10.1016\/j.radonc.2025.111331_b0190","article-title":"Ultrasound-based artificial intelligence model for prediction of Ki-67 proliferation index in soft tissue tumors","author":"Dai","year":"2024","journal-title":"Acad Radiol"},{"key":"10.1016\/j.radonc.2025.111331_b0195","doi-asserted-by":"crossref","first-page":"900","DOI":"10.21037\/jgo-23-63","article-title":"NCAPG is transcriptionally regulated by CBX3 and activates the Wnt\/beta-catenin signaling pathway to promote proliferation and the cell cycle and inhibit apoptosis in colorectal cancer","volume":"14","author":"Yang","year":"2023","journal-title":"J Gastrointest Oncol"}],"container-title":["Radiotherapy and Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814025053356?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167814025053356?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T05:39:21Z","timestamp":1770269961000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167814025053356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":39,"alternative-id":["S0167814025053356"],"URL":"https:\/\/doi.org\/10.1016\/j.radonc.2025.111331","relation":{},"ISSN":["0167-8140"],"issn-type":[{"value":"0167-8140","type":"print"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The combined treatment with TOP-V122, a dual-acting NO-releasing PDE-5 inhibitor, and ionizing irradiation as a novel therapeutical strategy for colorectal carcinoma","name":"articletitle","label":"Article Title"},{"value":"Radiotherapy and Oncology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.radonc.2025.111331","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"111331"}}