{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:16:43Z","timestamp":1783441003149,"version":"3.54.6"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100012634","name":"Novocure Ltd","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012634","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011542","name":"Mayo Clinics Center for Clinical and Translational Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006827","name":"Florida Department of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006827","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cancer Letters"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.canlet.2026.218651","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T18:23:51Z","timestamp":1781461431000},"page":"218651","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Tumor Treating Fields (TTFields) potentiate cisplatin efficacy and remodel the transcriptional landscape in preclinical models of pancreatic ductal adenocarcinoma"],"prefix":"10.1016","volume":"656","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3579-4317","authenticated-orcid":false,"given":"Santanu","family":"Bhattacharya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7881-4971","authenticated-orcid":false,"given":"Ishita","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreyartha","family":"Mukherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari Krishnareddy","family":"Rachamalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Gaiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7899-8438","authenticated-orcid":false,"given":"Douaa","family":"Albelal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramcharan Singh","family":"Angom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enfeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamit","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navnita","family":"Dutta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Story","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debabrata","family":"Mukhopadhyay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani M.","family":"Babiker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.canlet.2026.218651_bib1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.canlet.2026.218651_bib2","doi-asserted-by":"crossref","first-page":"2913","DOI":"10.1158\/0008-5472.CAN-14-0155","article-title":"Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States","volume":"74","author":"Rahib","year":"2014","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218651_bib3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1470-2045(23)00516-8","article-title":"Treatment of metastatic pancreatic cancer: 25 years of innovation with little progress for patients","volume":"25","author":"Gyawali","year":"2024","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib4","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","article-title":"Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine","volume":"369","author":"Von Hoff","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib5","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","article-title":"FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer","volume":"364","author":"Conroy","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib6","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1001\/jamaoncol.2019.3394","article-title":"Response rate following albumin-bound paclitaxel plus gemcitabine plus cisplatin treatment among patients with advanced pancreatic cancer: a phase 1b\/2 pilot clinical trial","volume":"6","author":"Jameson","year":"2020","journal-title":"JAMA Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib7","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1093\/neuonc\/now182","article-title":"Tumor treating fields: a novel treatment modality and its use in brain tumors","volume":"18","author":"Hottinger","year":"2016","journal-title":"Neuro Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1158\/1078-0432.CCR-17-1117","article-title":"Tumor-treating fields: a fourth modality in cancer treatment","volume":"24","author":"Mun","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218651_bib9","doi-asserted-by":"crossref","first-page":"3650","DOI":"10.1158\/0008-5472.CAN-22-0887","article-title":"The mechanisms of action of tumor treating fields","volume":"82","author":"Moser","year":"2022","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218651_bib10","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1200\/JCO-25-00746","article-title":"Tumor treating fields with gemcitabine and nab-paclitaxel for locally advanced pancreatic adenocarcinoma: randomized, open-label, pivotal phase III PANOVA-3 study","volume":"43","author":"Babiker","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/cgt.2016.71","article-title":"Acquired resistance of pancreatic cancer cells to cisplatin is multifactorial with cell context-dependent involvement of resistance genes","volume":"23","author":"Mezencev","year":"2016","journal-title":"Cancer Gene Ther."},{"key":"10.1016\/j.canlet.2026.218651_bib12","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13014-017-0941-6","article-title":"Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells","volume":"12","author":"Giladi","year":"2017","journal-title":"Radiat. Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib13","doi-asserted-by":"crossref","DOI":"10.3791\/55820","article-title":"Determining the optimal inhibitory frequency for cancerous cells using tumor treating fields (TTFields)","author":"Porat","year":"2017","journal-title":"JoVE J."},{"key":"10.1016\/j.canlet.2026.218651_bib14","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3390\/jfb16050160","article-title":"Tumor-treating fields alter nanomechanical properties of pancreatic ductal adenocarcinoma cells Co-Cultured with extracellular matrix","volume":"16","author":"Kulkarni","year":"2025","journal-title":"J. Funct. Biomater."},{"key":"10.1016\/j.canlet.2026.218651_bib15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.pan.2013.11.009","article-title":"Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields","volume":"14","author":"Giladi","year":"2014","journal-title":"Pancreatology"},{"key":"10.1016\/j.canlet.2026.218651_bib16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3389\/fphar.2020.00343","article-title":"The drug-resistance mechanisms of five platinum-based antitumor agents","volume":"11","author":"Zhou","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.canlet.2026.218651_bib17","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.1158\/1078-0432.CCR-16-2186","article-title":"A combination RNAi-Chemotherapy layer-by-layer nanoparticle for systemic targeting of KRAS\/P53 with cisplatin to treat non\u2013small cell lung cancer","volume":"23","author":"Gu","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.canlet.2026.218651_bib18","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1186\/s12967-024-05528-6","article-title":"Insights into gemcitabine resistance in pancreatic cancer: association with metabolic reprogramming and TP53 pathogenicity in patient derived xenografts","volume":"22","author":"Konat\u00e9","year":"2024","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib19","unstructured":"SEER\/NCI. Accessed October\/16\/2025 (2025)."},{"key":"10.1016\/j.canlet.2026.218651_bib20","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a031435","article-title":"KRAS: the critical driver and therapeutic target for pancreatic cancer","volume":"8","author":"Waters","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib21","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.3390\/cimb46040177","article-title":"Significance of TP53, CDKN2A, SMAD4 and KRAS in pancreatic cancer","volume":"46","author":"Stefanoudakis","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"10.1016\/j.canlet.2026.218651_bib22","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41419-022-05351-1","article-title":"Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.canlet.2026.218651_bib23","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.751311","article-title":"The PDAC extracellular matrix: a review of the ECM protein composition, tumor cell interaction, and therapeutic strategies","volume":"11","author":"Perez","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib24","doi-asserted-by":"crossref","DOI":"10.1158\/1538-7445.AM2025-2176","article-title":"Abstract 2176: tumor treating fields (TTFields) together with gemcitabine and nab-paclitaxel (Gem\/NabP) are effective against pancreatic ductal adenocarcinoma (PDAC), in vitro and in vivo","volume":"85","author":"Kan","year":"2025","journal-title":"Cancer Res."},{"key":"10.1016\/j.canlet.2026.218651_bib25","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.622509","article-title":"Exhausted CD8+T cells in the tumor immune microenvironment: new pathways to therapy","volume":"11","author":"Jiang","year":"2021","journal-title":"Front. Immunol."},{"key":"10.1016\/j.canlet.2026.218651_bib26","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1016\/j.cell.2024.06.036","article-title":"Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8+ T cells to promote antitumor immunity","volume":"187","author":"Cillo","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.canlet.2026.218651_bib27","article-title":"CD8+ T cell exhaustion and its regulatory mechanisms in the tumor microenvironment: key to the success of immunotherapy","volume":"15","author":"Zhang","year":"2024","journal-title":"Front. Immunol."},{"key":"10.1016\/j.canlet.2026.218651_bib28","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1158\/2326-6066.CIR-18-0750","article-title":"Coexpression of inhibitory receptors enriches for activated and functional CD8+ T cells in murine syngeneic tumor models","volume":"7","author":"Xiong","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"10.1016\/j.canlet.2026.218651_bib29","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12967-024-05002-3","article-title":"Diffuse large B-cell lymphoma: the significance of CD8+ tumor-infiltrating lymphocytes exhaustion mediated by TIM3\/Galectin-9 pathway","volume":"22","author":"Zhu","year":"2024","journal-title":"J. Transl. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib30","article-title":"Analysis of PD1, LAG3, TIGIT, and TIM3 expression in human lung adenocarcinoma reveals a 25-gene signature predicting immunotherapy response","volume":"5","author":"Gu\u00e9gan","year":"2024","journal-title":"Cell Rep. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib31","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/CJI.0000000000000122","article-title":"Targeting PD-1 and Tim-3 pathways to reverse CD8 T-Cell exhaustion and enhance Ex vivo T-Cell responses to autologous dendritic\/tumor vaccines","volume":"39","author":"Liu","year":"2016","journal-title":"J. Immunother."},{"key":"10.1016\/j.canlet.2026.218651_bib32","article-title":"Soluble Tim-3 serves as a tumor prognostic marker and therapeutic target for CD8(+) T cell exhaustion and anti-PD-1 resistance","volume":"5","author":"Chen","year":"2024","journal-title":"Cell Rep. Med."},{"key":"10.1016\/j.canlet.2026.218651_bib33","first-page":"319","volume":"vol. 11","author":"Wainer-Katsir","year":"2025"},{"key":"10.1016\/j.canlet.2026.218651_bib34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41467-017-02731-6","article-title":"Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis","volume":"9","author":"Kim","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.canlet.2026.218651_bib35","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.749673","article-title":"Upregulation of HSPA1A\/HSPA1B\/HSPA7 and downregulation of HSPA9 were related to poor survival in Colon cancer","volume":"11","author":"Guan","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib36","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.52707","article-title":"The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies","volume":"9","author":"Diaz","year":"2020","journal-title":"eLife"},{"key":"10.1016\/j.canlet.2026.218651_bib37","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.canlet.2026.218651_bib38","doi-asserted-by":"crossref","first-page":"33765","DOI":"10.18632\/oncotarget.9260","article-title":"Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2- and Tr1-biased T-cell immunity","volume":"7","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.canlet.2026.218651_bib39","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-16341-6","article-title":"Tumor treating fields suppress tumor cell growth and induce immunogenic cell death biomarkers in biliary tract cancer cell lines","volume":"15","author":"Yue","year":"2025","journal-title":"Sci. Rep."},{"key":"10.1016\/j.canlet.2026.218651_bib40","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1007\/s00262-020-02534-7","article-title":"Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy","volume":"69","author":"Voloshin","year":"2020","journal-title":"Cancer Immunol. Immunother."},{"key":"10.1016\/j.canlet.2026.218651_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.medj.2025.100708","article-title":"Efficacy and safety of adjuvant TTFields plus pembrolizumab and temozolomide in newly diagnosed glioblastoma: a phase 2 study","volume":"6","author":"Chen","year":"2025","journal-title":"Med"},{"key":"10.1016\/j.canlet.2026.218651_bib42","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2018.00033","article-title":"Olfactory receptors as biomarkers in human breast carcinoma tissues","volume":"8","author":"Weber","year":"2018","journal-title":"Front. Oncol."},{"key":"10.1016\/j.canlet.2026.218651_bib43","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41419-025-07546-8","article-title":"Role of the PI3K\/AKT signaling pathway in the cellular response to tumor treating fields (TTFields)","volume":"16","author":"Klein-Goldberg","year":"2025","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.canlet.2026.218651_bib44","doi-asserted-by":"crossref","first-page":"119","DOI":"10.5625\/lar.2017.33.2.119","article-title":"Use of C57BL\/6N mice on the variety of immunological researches","volume":"33","author":"Song","year":"2017","journal-title":"Lab. Anim. Res."}],"container-title":["Cancer Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526004143?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0304383526004143?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:24:46Z","timestamp":1783437886000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0304383526004143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":44,"alternative-id":["S0304383526004143"],"URL":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218651","relation":{},"ISSN":["0304-3835"],"issn-type":[{"value":"0304-3835","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Tumor Treating Fields (TTFields) potentiate cisplatin efficacy and remodel the transcriptional landscape in preclinical models of pancreatic ductal adenocarcinoma","name":"articletitle","label":"Article Title"},{"value":"Cancer Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.canlet.2026.218651","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"218651"}}