{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:09:48Z","timestamp":1792069788188,"version":"4.4.0"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100017521","name":"ESTEVE","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017521","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cancertreatmentreviews.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Treatment Reviews"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.ctrv.2026.103140","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T05:39:26Z","timestamp":1776577166000},"page":"103140","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Streptozotocin revisited: Pharmacological determinants supporting new scheduling strategies in neuroendocrine tumours"],"prefix":"10.1016","volume":"146","author":[{"given":"Nicola","family":"Fazio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3642-0798","authenticated-orcid":false,"given":"Francesca","family":"Spada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Benini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Mulargiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Del Re","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romano","family":"Danesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.ctrv.2026.103140_b0005","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1007\/s001250051564","article-title":"Relative importance of transport and alkylation for pancreatic beta-cell toxicity of streptozotocin","volume":"43","author":"Elsner","year":"2000","journal-title":"Diabetologia"},{"issue":"12","key":"10.1016\/j.ctrv.2026.103140_b0010","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1159\/000524988","article-title":"Streptozotocin, 1982-2022: forty Years from the FDA's approval to treat pancreatic neuroendocrine tumors","volume":"112","author":"Capdevila","year":"2022","journal-title":"Neuroendocrinology"},{"issue":"3","key":"10.1016\/j.ctrv.2026.103140_b0015","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11523-012-0224-y","article-title":"Streptozocin-based chemotherapy is not history in neuroendocrine tumours","volume":"7","author":"Weatherstone","year":"2012","journal-title":"Target Oncol"},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0020","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s12020-021-02859-y","article-title":"Streptozocin\/5-fluorouracil chemotherapy of pancreatic neuroendocrine tumours in the era of targeted therapy","volume":"75","author":"Lahner","year":"2022","journal-title":"Endocrine"},{"issue":"9","key":"10.1016\/j.ctrv.2026.103140_b0025","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.3390\/jcm8091332","article-title":"Sugar-lowering drugs for type 2 diabetes mellitus and metabolic syndrome-strategies for in vivo administration: Part-II","volume":"8","author":"Vieira","year":"2019","journal-title":"J Clin Med"},{"issue":"4","key":"10.1016\/j.ctrv.2026.103140_b0030","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1159\/000430816","article-title":"Temozolomide in advanced neuroendocrine neoplasms: pharmacological and clinical aspects","volume":"101","author":"Koumarianou","year":"2015","journal-title":"Neuroendocrinology"},{"issue":"5","key":"10.1016\/j.ctrv.2026.103140_b0035","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1006\/bbrc.2001.6145","article-title":"Differential sensitivity of GLUT1- and GLUT2-expressing beta cells to streptozotocin","volume":"289","author":"Hosokawa","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"issue":"2","key":"10.1016\/j.ctrv.2026.103140_b0040","doi-asserted-by":"crossref","first-page":"E326","DOI":"10.1152\/ajpendo.00296.2007","article-title":"KATP channel-deficient pancreatic beta-cells are streptozotocin resistant because of lower GLUT2 activity","volume":"294","author":"Xu","year":"2008","journal-title":"Am J Phys Endocrinol Metab"},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0045","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3390\/cells12010094","article-title":"Kidney proximal tubule GLUT2-more than meets the eye","volume":"12","author":"Ahmad","year":"2022","journal-title":"Cells"},{"issue":"3","key":"10.1016\/j.ctrv.2026.103140_b0195","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3390\/cells11030492","article-title":"Pathogenic mechanism of autoimmune diabetes mellitus in humans: potential role of streptozotocin-induced selective autoimmunity against human islet \u03b2-cells","volume":"11","author":"Zhu","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.ctrv.2026.103140_b0220","doi-asserted-by":"crossref","DOI":"10.1016\/j.molstruc.2020.128381","article-title":"Novel strategies of Raman imaging for monitoring the therapeutic benefit of temozolomide in glioblastoma","volume":"1217","author":"Imiela","year":"2020","journal-title":"J Mol Structure"},{"issue":"5","key":"10.1016\/j.ctrv.2026.103140_b0050","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/BF01219512","article-title":"Streptozotocin: its excretion and metabolism in the rat","volume":"12","author":"Karunanayake","year":"1976","journal-title":"Diabetologia"},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0055","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/2251-6581-12-60","article-title":"Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans","volume":"12","author":"Eleazu","year":"2013","journal-title":"J Diabetes Metab Disord"},{"issue":"5","key":"10.1016\/j.ctrv.2026.103140_b0060","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.ejca.2013.12.011","article-title":"Capecitabine and streptozocin \u00b1 cisplatin in advanced gastroenteropancreatic neuroendocrine tumours","volume":"50","author":"Meyer","year":"2014","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.ctrv.2026.103140_b0065","unstructured":"Zanosar. https:\/\/www.medicines.org.uk\/emc\/product\/9877\/smpc\/print."},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0070","doi-asserted-by":"crossref","first-page":"122","DOI":"10.7326\/0003-4819-96-1-122_1","article-title":"Nephrotoxicity of streptozocin","volume":"96","author":"Perry","year":"1982","journal-title":"Ann Intern Med"},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0075","doi-asserted-by":"crossref","first-page":"8705","DOI":"10.1038\/s41598-023-35850-w","article-title":"Streptozotocin induces renal proximal tubular injury through p53 signaling activation","volume":"13","author":"Nakai","year":"2023","journal-title":"Sci Rep"},{"issue":"4","key":"10.1016\/j.ctrv.2026.103140_b0080","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1177\/0023677219872224","article-title":"Optimising streptozotocin dosing to minimise renal toxicity and impairment of stomach emptying in male 129\/Sv mice","volume":"54","author":"N\u00f8rgaard","year":"2020","journal-title":"Lab Anim"},{"issue":"2\u20133","key":"10.1016\/j.ctrv.2026.103140_b0085","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S1383-5742(02)00044-3","article-title":"Genotoxicity of streptozotocin","volume":"512","author":"Bolz\u00e1n","year":"2002","journal-title":"Mutat Res"},{"issue":"21","key":"10.1016\/j.ctrv.2026.103140_b0090","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1056\/NEJM198011203032101","article-title":"Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma","volume":"303","author":"Moertel","year":"1980","journal-title":"N Engl J Med"},{"issue":"9","key":"10.1016\/j.ctrv.2026.103140_b0095","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1002\/1097-0142(19900501)65:9<1883::AID-CNCR2820650902>3.0.CO;2-3","article-title":"Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors","volume":"65","author":"Eriksson","year":"1990","journal-title":"Cancer"},{"issue":"8","key":"10.1016\/j.ctrv.2026.103140_b0100","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1056\/NEJM199202203260804","article-title":"Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma","volume":"326","author":"Moertel","year":"1992","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ctrv.2026.103140_b0105","unstructured":"Two Chemotherapy Regimens Plus or Minus Bevacizumab (BETTER2). https:\/\/clinicaltrials.gov\/study\/NCT03351296."},{"issue":"38","key":"10.1016\/j.ctrv.2026.103140_b0110","doi-asserted-by":"crossref","first-page":"27200","DOI":"10.1074\/jbc.M113.469486","article-title":"Phlorizin pretreatment reduces acute renal toxicity in a mouse model for diabetic nephropathy","volume":"288","author":"Brouwers","year":"2013","journal-title":"J Biol Chem"},{"issue":"8","key":"10.1016\/j.ctrv.2026.103140_b0115","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1200\/JCO.23.02724","article-title":"\u201cGroupe d\u2019\u00e9tude des tumeurs endocrines (GTE)\u201d and the French ENDOCAN-RENATEN network. Oxaliplatin-based Versus Alkylating Agent in Neuroendocrine Tumors according to the O6-methylguanine-DNA Methyltransferase Status: a Randomized phase II Study (MGMT-NET)","volume":"43","author":"Walter","year":"2025","journal-title":"J Clin Oncol"},{"issue":"3","key":"10.1016\/j.ctrv.2026.103140_b0120","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s11154-021-09638-0","article-title":"Chemotherapy in NEN: still has a role?","volume":"22","author":"Espinosa-Olarte","year":"2021","journal-title":"Rev Endocr Metab Disord"},{"issue":"12","key":"10.1016\/j.ctrv.2026.103140_b0125","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1016\/S1470-2045(21)00572-6","volume":"22","author":"Strosberg","year":"2021","journal-title":"Lancet Oncol"},{"issue":"7","key":"10.1016\/j.ctrv.2026.103140_b0130","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1200\/JCO.22.01013","article-title":"Randomized Study of Temozolomide or Temozolomide and Capecitabine in patients with Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211)","volume":"41","author":"Kunz","year":"2023","journal-title":"J Clin Oncol"},{"issue":"2","key":"10.1016\/j.ctrv.2026.103140_b0135","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1056\/NEJMoa1607427","article-title":"NETTER-1 Trial investigators. phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors","volume":"376","author":"Strosberg","year":"2017","journal-title":"N Engl J Med"},{"issue":"10446","key":"10.1016\/j.ctrv.2026.103140_b0140","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1016\/S0140-6736(24)00701-3","volume":"403","author":"Singh","year":"2024","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.ctrv.2026.103140_b0145","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1056\/NEJMoa1009290","article-title":"RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors","volume":"364","author":"Yao","year":"2011","journal-title":"N Engl J Med"},{"issue":"6","key":"10.1016\/j.ctrv.2026.103140_b0150","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1056\/NEJMoa1003825","article-title":"Sunitinib malate for the treatment of pancreatic neuroendocrine tumors","volume":"364","author":"Raymond","year":"2011","journal-title":"N Engl J Med"},{"issue":"7","key":"10.1016\/j.ctrv.2026.103140_b0155","first-page":"2786","article-title":"Alkylation of DNA in rat tissues following administration of streptozotocin","volume":"41","author":"Bennett","year":"1981","journal-title":"Cancer Res"},{"issue":"19","key":"10.1016\/j.ctrv.2026.103140_b0160","doi-asserted-by":"crossref","first-page":"10764","DOI":"10.1073\/pnas.96.19.10764","article-title":"Role of DNA mismatch repair and p53 in signaling induction of apoptosis by alkylating agents","volume":"96","author":"Hickman","year":"1999","journal-title":"PNAS"},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0165","doi-asserted-by":"crossref","first-page":"168","DOI":"10.4161\/cc.9.1.10363","article-title":"Processing of O6-methylguanine into DNA double-strand breaks requires two rounds of replication whereas apoptosis is also induced in subsequent cell cycles","volume":"9","author":"Quiros","year":"2010","journal-title":"Cell Cycle"},{"key":"10.1016\/j.ctrv.2026.103140_b0170","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.69544","article-title":"Crosstalk between repair pathways elicits double-strand breaks in alkylated DNA and implications for the action of temozolomide","volume":"10","author":"Fuchs","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.ctrv.2026.103140_b0175","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0079-6603(01)68088-7","article-title":"BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis","volume":"68","author":"Kaina","year":"2001","journal-title":"Prog Nucleic Acid Res Mol Biol"},{"issue":"12","key":"10.1016\/j.ctrv.2026.103140_b0180","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.5858\/arpa.2010-0560-OA","article-title":"Loss of expression of DNA mismatch repair proteins is rare in pancreatic and small intestinal neuroendocrine tumors","volume":"135","author":"Arnason","year":"2011","journal-title":"Arch Pathol Lab Med"},{"issue":"2","key":"10.1016\/j.ctrv.2026.103140_b0185","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1007\/s12022-020-09612-7","article-title":"Homogeneous MMR deficiency throughout the entire tumor mass occurs in a subset of colorectal neuroendocrine carcinomas","volume":"31","author":"Fraune","year":"2020","journal-title":"Endocr Pathol"},{"issue":"1","key":"10.1016\/j.ctrv.2026.103140_b0190","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1530\/ERC-14-0410","article-title":"Microsatellite unstable gastrointestinal neuroendocrine carcinomas: a new clinicopathologic entity","volume":"22","author":"Sahnane","year":"2015","journal-title":"Endocr Relat Cancer"},{"issue":"12","key":"10.1016\/j.ctrv.2026.103140_b0200","doi-asserted-by":"crossref","DOI":"10.1111\/jne.13343","article-title":"European Neuroendocrine Tumour Society (ENETS) 2023 guidance paper for nonfunctioning pancreatic neuroendocrine tumours","volume":"35","author":"Kos-Kud\u0142a","year":"2023","journal-title":"J Neuroendocrinol"},{"issue":"4","key":"10.1016\/j.ctrv.2026.103140_b0205","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000028610","article-title":"Long-term treatment with streptozocin\/5-fluorouracil chemotherapy in patients with metastatic pancreatic neuroendocrine tumors: Case series","volume":"101","author":"M\u00fcller","year":"2022","journal-title":"Medicine (Baltimore)"},{"key":"10.1016\/j.ctrv.2026.103140_b0210","article-title":"Predictive Factors of Response to Streptozotocin in Neuroendocrine Pancreatic Neoplasms","volume":"12(24):7557","author":"Fanciulli G, La Salvia A, Di Molfetta S, Cannavale G, Puliani G, Verrico M, Campolo F, Colao A, Faggiano A, Nike Group","year":"2023","journal-title":"J Clin Med"},{"key":"10.1016\/j.ctrv.2026.103140_b0215","series-title":"Presented at: 22nd Annual Meeting of the UK and Ireland Neuroendocrine Tumour Society","article-title":"Clinical outcomes of streptozocin (STZ) based chemotherapy in neuroendocrine tumours (NETs): a retrospective analysis of 26 patients from a single cancer centre \u2013 Nottingham University Hospitals (UK)","author":"Arora","year":"2024"}],"container-title":["Cancer Treatment Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030573722600054X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S030573722600054X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T02:08:37Z","timestamp":1778292517000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S030573722600054X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":44,"alternative-id":["S030573722600054X"],"URL":"https:\/\/doi.org\/10.1016\/j.ctrv.2026.103140","relation":{},"ISSN":["0305-7372"],"issn-type":[{"value":"0305-7372","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Streptozotocin revisited: Pharmacological determinants supporting new scheduling strategies in neuroendocrine tumours","name":"articletitle","label":"Article Title"},{"value":"Cancer Treatment Reviews","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ctrv.2026.103140","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"103140"}}