{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T16:46:58Z","timestamp":1776271618177,"version":"3.50.1"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T00:00:00Z","timestamp":1727481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T00:00:00Z","timestamp":1727481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministerstwo Edukacji i Nauki","doi-asserted-by":"publisher","award":["FS200\/1WP\/LK\/1"],"award-info":[{"award-number":["FS200\/1WP\/LK\/1"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose<\/jats:title>\n                <jats:p>Pancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan\u2013Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4\u20137). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8\u20137.8) vs. 6.7 months (95% CI 6.4\u20137.0) for patients who did not have additional treatment (p\u2009&lt;\u20090.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7\u201311.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5\u20138.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p\u2009=\u20090.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9\u201322%) and 14.8% (95% CI 11.1\u201319.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2\u20134.4%).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-024-05962-5","type":"journal-article","created":{"date-parts":[[2024,9,28]],"date-time":"2024-09-28T13:02:22Z","timestamp":1727528542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer"],"prefix":"10.1007","volume":"150","author":[{"given":"Leszek","family":"Kraj","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Chmiel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"\u015aliwczy\u0144ski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141ukasz","family":"Szyma\u0144ski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Wo\u017aniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maciej","family":"S\u0142odkowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Stok\u0142osa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucjan","family":"Wyrwicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,9,28]]},"reference":[{"key":"5962_CR1","doi-asserted-by":"crossref","unstructured":"Al-Shamsi HO et al (2016) Prognostic effect of angiotensin-converting-enzyme inhibitors (ACEI) and diuretics in patients with pancreatic cancer. J Clin Oncol 34(4_suppl): 420\u2013420","DOI":"10.1200\/jco.2016.34.4_suppl.420"},{"issue":"16","key":"5962_CR2","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1200\/JCO.2015.63.3511","volume":"34","author":"R Chaiteerakij","year":"2016","unstructured":"Chaiteerakij R et al (2016) Metformin use and survival of patients with pancreatic cancer: a cautionary lesson. J Clin Oncol 34(16):1898\u20131904","journal-title":"J Clin Oncol"},{"issue":"1","key":"5962_CR3","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1002\/cam4.2705","volume":"9","author":"KKW Chan","year":"2020","unstructured":"Chan KKW et al (2020) Real-world outcomes of FOLFIRINOX vs gemcitabine and nab-paclitaxel in advanced pancreatic cancer: a population-based propensity score-weighted analysis. Cancer Med 9(1):160\u2013169","journal-title":"Cancer Med"},{"key":"5962_CR4","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1038\/ncomms3516","volume":"4","author":"VP Chauhan","year":"2013","unstructured":"Chauhan VP et al (2013) Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat Commun 4:2516","journal-title":"Nat Commun"},{"issue":"1","key":"5962_CR5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ccr.2014.06.003","volume":"26","author":"VP Chauhan","year":"2014","unstructured":"Chauhan VP et al (2014) Compression of pancreatic tumor blood vessels by hyaluronan is caused by solid stress and not interstitial fluid pressure. Cancer Cell 26(1):14\u201315","journal-title":"Cancer Cell"},{"issue":"1","key":"5962_CR6","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.bbrc.2015.07.118","volume":"465","author":"G Cheng","year":"2015","unstructured":"Cheng G, Lanza-Jacoby S (2015) Metformin decreases growth of pancreatic cancer cells by decreasing reactive oxygen species: Role of NOX4. Biochem Biophys Res Commun 465(1):41\u201346","journal-title":"Biochem Biophys Res Commun"},{"issue":"19","key":"5962_CR7","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","volume":"364","author":"T Conroy","year":"2011","unstructured":"Conroy T et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817\u20131825","journal-title":"N Engl J Med"},{"issue":"11","key":"5962_CR8","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.annonc.2023.08.009","volume":"34","author":"T Conroy","year":"2023","unstructured":"Conroy T et al (2023) Pancreatic cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up<sup>\u2606<\/sup>. Ann Oncol 34(11):987\u20131002","journal-title":"Ann Oncol"},{"key":"5962_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118518","volume":"262","author":"HA El-Mahdy","year":"2020","unstructured":"El-Mahdy HA et al (2020) Diltiazem potentiates the cytotoxicity of gemcitabine and 5-fluorouracil in PANC-1 human pancreatic cancer cells through inhibition of P-glycoprotein. Life Sci 262:118518","journal-title":"Life Sci"},{"key":"5962_CR10","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.annonc.2021.05.117","volume":"32","author":"C Flores","year":"2021","unstructured":"Flores C et al (2021) P-62 Overall survival of patients with pancreatic cancer. Ann Oncol 32:S117\u2013S118","journal-title":"Ann Oncol"},{"issue":"3","key":"5962_CR11","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.hpb.2023.12.001","volume":"26","author":"ZV Fong","year":"2024","unstructured":"Fong ZV et al (2024) Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection. HPB 26(3):418\u2013425","journal-title":"HPB"},{"issue":"8","key":"5962_CR12","volume":"13","author":"M Gyawali","year":"2021","unstructured":"Gyawali M et al (2021) Magic of a common sugar pill in cancer: can metformin raise survival in pancreatic cancer patients? Cureus 13(8):e16916","journal-title":"Cureus"},{"issue":"12","key":"5962_CR13","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1038\/s41440-022-01038-4","volume":"45","author":"A Hirata","year":"2022","unstructured":"Hirata A et al (2022) Increased risk of metastasis in patients with incidental use of renin-angiotensin system inhibitors: a retrospective analysis for multiple types of cancer based on electronic medical records. Hypertens Res 45(12):1869\u20131881","journal-title":"Hypertens Res"},{"issue":"8","key":"5962_CR14","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1158\/2159-8290.CD-15-1177","volume":"6","author":"J Incio","year":"2016","unstructured":"Incio J et al (2016) Obesity-Induced inflammation and desmoplasia promote pancreatic cancer progression and resistance to chemotherapy. Cancer Discov 6(8):852\u2013869","journal-title":"Cancer Discov"},{"issue":"6","key":"5962_CR15","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1111\/nep.13706","volume":"25","author":"KJ Jager","year":"2020","unstructured":"Jager KJ et al (2020) Where to look for the most frequent biases? Nephrology (Carlton) 25(6):435\u2013441","journal-title":"Nephrology (Carlton)"},{"key":"5962_CR16","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3389\/fonc.2018.00055","volume":"8","author":"M Kalli","year":"2018","unstructured":"Kalli M, Stylianopoulos T (2018) Defining the role of solid stress and matrix stiffness in cancer cell proliferation and metastasis. Front Oncol 8:55","journal-title":"Front Oncol"},{"issue":"2","key":"5962_CR17","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/s41440-022-01041-9","volume":"46","author":"A Kaneyama","year":"2023","unstructured":"Kaneyama A et al (2023) Impact of hypertension and diabetes on the onset of chronic kidney disease in a general Japanese population. Hypertens Res 46(2):311\u2013320","journal-title":"Hypertens Res"},{"issue":"282","key":"5962_CR18","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1080\/01621459.1958.10501452","volume":"53","author":"EL Kaplan","year":"1958","unstructured":"Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Statist Assoc 53(282):457","journal-title":"J Am Statist Assoc"},{"issue":"1","key":"5962_CR19","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12885-022-09200-4","volume":"22","author":"SW Keith","year":"2022","unstructured":"Keith SW et al (2022) Angiotensin blockade therapy and survival in pancreatic cancer: a population study. BMC Cancer 22(1):150","journal-title":"BMC Cancer"},{"key":"5962_CR20","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119118","volume":"270","author":"N Khoshghamat","year":"2021","unstructured":"Khoshghamat N et al (2021) The therapeutic potential of renin-angiotensin system inhibitors in the treatment of pancreatic cancer. Life Sci 270:119118","journal-title":"Life Sci"},{"issue":"7","key":"5962_CR21","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S1470-2045(15)00027-3","volume":"16","author":"S Kordes","year":"2015","unstructured":"Kordes S et al (2015) Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol 16(7):839\u2013847","journal-title":"Lancet Oncol"},{"key":"5962_CR22","doi-asserted-by":"crossref","unstructured":"Kraj L et al (2017) Calcium channel blockers use and overall survival in pancreatic cancer patients receiving gemcitabine. J Clin Oncol 35(15_suppl):e15756-e15756","DOI":"10.1200\/JCO.2017.35.15_suppl.e15756"},{"issue":"1","key":"5962_CR23","doi-asserted-by":"publisher","first-page":"5825","DOI":"10.1038\/s41598-017-06207-x","volume":"7","author":"X Li","year":"2017","unstructured":"Li X et al (2017) The effect of metformin on survival of patients with pancreatic cancer: a meta-analysis. Sci Rep 7(1):5825","journal-title":"Sci Rep"},{"issue":"19","key":"5962_CR24","doi-asserted-by":"publisher","first-page":"5959","DOI":"10.1158\/1078-0432.CCR-17-0256","volume":"23","author":"H Liu","year":"2017","unstructured":"Liu H et al (2017) Use of angiotensin system inhibitors is associated with immune activation and longer survival in nonmetastatic pancreatic ductal adenocarcinoma. Clin Cancer Res 23(19):5959\u20135969","journal-title":"Clin Cancer Res"},{"issue":"5","key":"5962_CR25","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/s41433-021-01897-0","volume":"36","author":"A Miroshnychenko","year":"2022","unstructured":"Miroshnychenko A et al (2022) Cohort studies investigating the effects of exposures: key principles that impact the credibility of the results. Eye 36(5):905\u2013906","journal-title":"Eye"},{"issue":"7","key":"5962_CR26","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1001\/jamaoncol.2019.0892","volume":"5","author":"JE Murphy","year":"2019","unstructured":"Murphy JE et al (2019) Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a Phase 2 Clinical Trial. JAMA Oncol 5(7):1020\u20131027","journal-title":"JAMA Oncol"},{"issue":"11","key":"5962_CR27","doi-asserted-by":"publisher","first-page":"1644","DOI":"10.1038\/sj.bjc.6605955","volume":"103","author":"Y Nakai","year":"2010","unstructured":"Nakai Y et al (2010) Inhibition of renin\u2013angiotensin system affects prognosis of advanced pancreatic cancer receiving gemcitabine. Br J Cancer 103(11):1644\u20131648","journal-title":"Br J Cancer"},{"issue":"8","key":"5962_CR28","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1111\/j.1349-7006.2012.02311.x","volume":"103","author":"Y Nakai","year":"2012","unstructured":"Nakai Y et al (2012) Phase I trial of gemcitabine and candesartan combination therapy in normotensive patients with advanced pancreatic cancer: GECA1. Cancer Sci 103(8):1489\u20131492","journal-title":"Cancer Sci"},{"issue":"5","key":"5962_CR29","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1007\/s10637-013-9972-5","volume":"31","author":"Y Nakai","year":"2013","unstructured":"Nakai Y et al (2013) A multicenter phase II trial of gemcitabine and candesartan combination therapy in patients with advanced pancreatic cancer: GECA2. Invest New Drugs 31(5):1294\u20131299","journal-title":"Invest New Drugs"},{"issue":"2","key":"5962_CR30","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.pan.2023.01.007","volume":"23","author":"Z Nowicka","year":"2023","unstructured":"Nowicka Z et al (2023) Metanalyses on metformin\u2019s role in pancreatic cancer suffer from severe bias and low data quality - An umbrella review. Pancreatology 23(2):192\u2013200","journal-title":"Pancreatology"},{"issue":"18","key":"5962_CR31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2200143119","volume":"119","author":"DR Principe","year":"2022","unstructured":"Principe DR et al (2022) Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer. Proc Natl Acad Sci 119(18):e2200143119","journal-title":"Proc Natl Acad Sci"},{"key":"5962_CR32","unstructured":"R Core Team (2023) R: A language and environment for statistical computing. 2023\u201310\u201325]; Available from: https:\/\/www.R-project.org\/."},{"issue":"5","key":"5962_CR33","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1158\/1078-0432.CCR-15-1722","volume":"22","author":"M Reni","year":"2016","unstructured":"Reni M et al (2016) (Ir)relevance of metformin treatment in patients with metastatic pancreatic cancer: an open-label, randomized Phase II Trial. Clin Cancer Res 22(5):1076\u20131085","journal-title":"Clin Cancer Res"},{"issue":"10","key":"5962_CR34","doi-asserted-by":"publisher","first-page":"2905","DOI":"10.1158\/1078-0432.CCR-11-2994","volume":"18","author":"N Sadeghi","year":"2012","unstructured":"Sadeghi N et al (2012) Metformin use is associated with better survival of diabetic patients with pancreatic cancer. Clin Cancer Res 18(10):2905\u20132912","journal-title":"Clin Cancer Res"},{"issue":"37","key":"5962_CR35","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000021687","volume":"99","author":"YQ Shi","year":"2020","unstructured":"Shi YQ et al (2020) Relationships are between metformin use and survival in pancreatic cancer patients concurrent with diabetes: A systematic review and meta-analysis. Medicine (Baltimore) 99(37):e21687","journal-title":"Medicine (Baltimore)"},{"key":"5962_CR36","doi-asserted-by":"crossref","unstructured":"Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1): 7\u201334","DOI":"10.3322\/caac.21551"},{"issue":"5","key":"5962_CR37","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1053\/j.gastro.2023.02.012","volume":"164","author":"EM Stoffel","year":"2023","unstructured":"Stoffel EM, Brand RE, Goggins M (2023) Pancreatic cancer: changing epidemiology and new approaches to risk assessment, early detection, and prevention. Gastroenterology 164(5):752\u2013765","journal-title":"Gastroenterology"},{"key":"5962_CR38","doi-asserted-by":"crossref","unstructured":"Sung H et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: Cancer J Clin 71(3): 209\u2013249","DOI":"10.3322\/caac.21660"},{"issue":"1","key":"5962_CR39","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3390\/ph16010115","volume":"16","author":"I Szymczak-Pajor","year":"2023","unstructured":"Szymczak-Pajor I et al (2023) Metformin induces apoptosis in human Pancreatic Cancer (PC) cells accompanied by changes in the levels of histone acetyltransferases (Particularly, p300\/CBP-Associated Factor (PCAF) Protein Levels). Pharmaceuticals 16(1):115","journal-title":"Pharmaceuticals"},{"issue":"6","key":"5962_CR40","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1179\/1973947813Y.0000000150","volume":"26","author":"K Takakura","year":"2014","unstructured":"Takakura K et al (2014) Long-term management of gemcitabine in a patient with advanced pancreatic cancer undergoing haemodialysis. J Chemother 26(6):369\u2013372","journal-title":"J Chemother"},{"key":"5962_CR41","unstructured":"Therneau TM (2023) A Package for Survival Analysis in R. 2023 26.09.2023]; Available from: https:\/\/CRAN.R-project.org\/package=survival."},{"issue":"7","key":"5962_CR42","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1097\/CAD.0000000000000947","volume":"31","author":"SJ Tingle","year":"2020","unstructured":"Tingle SJ et al (2020) Calcium channel blockers in pancreatic cancer: increased overall survival in a retrospective cohort study. Anti-Cancer Drugs 31(7):737\u2013741","journal-title":"Anti-Cancer Drugs"},{"key":"5962_CR43","doi-asserted-by":"publisher","first-page":"175883592412470","DOI":"10.1177\/17588359241247019","volume":"16","author":"K-Y Tseng","year":"2024","unstructured":"Tseng K-Y et al (2024) The concomitant use of the renin\u2013angiotensin system inhibitors and survival outcomes of patients with pancreatic adenocarcinoma: an analysis from a tertiary center. Therap Adv Med Oncol 16:17588359241247020","journal-title":"Therap Adv Med Oncol"},{"key":"5962_CR44","doi-asserted-by":"crossref","unstructured":"van Eijck CWF et al (2024) Metformin boosts antitumor immunity and improves prognosis in upfront resected pancreatic cancer: an observational study. JNCI: J Natl Cancer Instit p. djae070","DOI":"10.1093\/jnci\/djae070"},{"issue":"18","key":"5962_CR45","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","volume":"369","author":"DD Von Hoff","year":"2013","unstructured":"Von Hoff DD et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691\u20131703","journal-title":"N Engl J Med"},{"issue":"2","key":"5962_CR46","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s13238-020-00760-4","volume":"12","author":"C Wang","year":"2021","unstructured":"Wang C et al (2021) Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation. Protein Cell 12(2):128\u2013144","journal-title":"Protein Cell"},{"issue":"10018","key":"5962_CR47","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S0140-6736(15)00986-1","volume":"387","author":"A Wang-Gillam","year":"2016","unstructured":"Wang-Gillam A et al (2016) Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet 387(10018):545\u2013557","journal-title":"Lancet"},{"issue":"15","key":"5962_CR48","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.1158\/1078-0432.CCR-14-1051","volume":"21","author":"CJ Whatcott","year":"2015","unstructured":"Whatcott CJ et al (2015) Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. Clin Cancer Res 21(15):3561\u20133568","journal-title":"Clin Cancer Res"},{"issue":"3","key":"5962_CR49","doi-asserted-by":"publisher","first-page":"338","DOI":"10.4103\/jomfp.JOMFP_136_19","volume":"23","author":"H Zainab","year":"2019","unstructured":"Zainab H, Sultana A (2019) Stromal desmoplasia as a possible prognostic indicator in different grades of oral squamous cell carcinoma. J Oral Maxillofac Pathol 23(3):338\u2013343","journal-title":"J Oral Maxillofac Pathol"},{"issue":"18","key":"5962_CR50","doi-asserted-by":"publisher","first-page":"4504","DOI":"10.3390\/ijms20184504","volume":"20","author":"S Zeng","year":"2019","unstructured":"Zeng S et al (2019) Chemoresistance in pancreatic cancer. Int J Mol Sci 20(18):4504","journal-title":"Int J Mol Sci"},{"key":"5962_CR51","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00282","author":"J Zhang","year":"2020","unstructured":"Zhang J et al (2020) Survival benefit of metformin use for pancreatic cancer patients who underwent pancreatectomy: results from a meta-analysis. Front Med. https:\/\/doi.org\/10.3389\/fmed.2020.00282","journal-title":"Front Med"},{"issue":"1","key":"5962_CR52","doi-asserted-by":"publisher","first-page":"99","DOI":"10.3892\/ijo.2016.3512","volume":"49","author":"L Zhao","year":"2016","unstructured":"Zhao L et al (2016) Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells. Int J Oncol 49(1):99\u2013110","journal-title":"Int J Oncol"},{"issue":"15","key":"5962_CR53","doi-asserted-by":"publisher","first-page":"25242","DOI":"10.18632\/oncotarget.15692","volume":"8","author":"P-T Zhou","year":"2017","unstructured":"Zhou P-T et al (2017) Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis. Oncotarget 8(15):25242\u201325250","journal-title":"Oncotarget"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05962-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-024-05962-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05962-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:02:53Z","timestamp":1728446573000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-024-05962-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,28]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["5962"],"URL":"https:\/\/doi.org\/10.1007\/s00432-024-05962-5","relation":{},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,28]]},"assertion":[{"value":"24 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}],"article-number":"434"}}