{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T05:21:10Z","timestamp":1791523270628,"version":"4.3.4"},"reference-count":96,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Social Fund"},{"name":"tax funds"},{"name":"Helmholtz Association"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous cancer with a severe stromal reaction mediated by pancreatic stellate cells (PSCs), leading to increased resistance to chemotherapy and radiotherapy. Following a repurposing concept, this preclinical study investigates the potential of approved drugs, known to be modulators of cellular copper transport, in combination with cisplatin for therapeutic approaches in PDAC. Two major strategies were pursued: (i) inhibiting copper transporters ATP7A and B with tranilast (TR) and omeprazole (OM) to block the cellular copper and, potentially, also cisplatin efflux, and (ii) using the chelator elesclomol (ES) to elevate intracellular copper and cisplatin levels. Human cell lines PanC-1 (PDAC), HPaSteC (PSC), and their co-culture, as well as the hepatocellular carcinoma cell line HepG2 as a reference model, were used. In addition to an analysis of the expression of copper transport proteins, the dynamics of cellular copper uptake and transport were monitored using a [64Cu]CuCl2 radiotracer approach. In vitro, all drugs enhanced cellular copper uptake and\/or reduced copper efflux. Moreover, all drugs contributed to the enhanced cellular anticancer activity of cisplatin, with ES being the most effective compound. The results suggest that the targeted modulation of copper transport mechanisms may offer novel adjuvant approaches for the treatment of PDAC.<\/jats:p>","DOI":"10.3390\/cells14191489","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T08:19:45Z","timestamp":1758701985000},"page":"1489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Investigation of the Putative Relationship Between Copper Transport and the Anticancer Activity of Cisplatin in Ductal Pancreatic Adenocarcinoma"],"prefix":"10.3390","volume":"14","author":[{"given":"Alina","family":"Doctor","sequence":"first","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Bergstrasse 66, 01069 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4550-0394","authenticated-orcid":false,"given":"Jonas","family":"Sch\u00e4dlich","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Bergstrasse 66, 01069 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-6000","authenticated-orcid":false,"given":"Sandra","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1610-1493","authenticated-orcid":false,"given":"Jens","family":"Pietzsch","sequence":"additional","affiliation":[{"name":"Department of Radiopharmaceutical and Chemical Biology, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany"},{"name":"Faculty of Chemistry and Food Chemistry, School of Science, Technische Universit\u00e4t Dresden, Bergstrasse 66, 01069 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","unstructured":"WCRF (2025, July 07). 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