{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:18:41Z","timestamp":1787170721746,"version":"build-2736575974"},"reference-count":71,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","award":["R20085MM"],"award-info":[{"award-number":["R20085MM"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004431","name":"Fondation de France","doi-asserted-by":"publisher","award":["R023044MM"],"award-info":[{"award-number":["R023044MM"]}],"id":[{"id":"10.13039\/501100004431","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>Despite advances in immunotherapy, doxorubicin (Dox) chemotherapy is still the irreplaceable first\u2010line therapy for solid tumours such as breast cancer. However, chemotherapy resistance is the major limiting factor, requiring the use of high doses of Dox to achieve the anti\u2010tumour actions, often leading to severe side effects. Unravelling the mechanisms behind chemoresistance and identifying potential biomarkers for mitigating this resistance could enhance current treatment strategies and improve patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>We developed human 3D breast cancer spheroids (HBCSs) as a model that closely mimics in vivo tumour structure and microenvironment. Given that hypoxia and elevated levels of the angiogenic cytokine, prokineticin\u20102 (PK2), are associated with chemoresistance to antiangiogenic therapy, we explored the effect of a hypoxia\u2010inducible factor (HIF\u20101\u03b1) inhibitor on viability defect in HBCSs and the levels of PK2 in the conditioned medium following Dox treatment. We also assessed levels of HIF\u20101\u03b1, active caspase\u20103, TUNEL and reactive oxygen species (ROS), and CD73 enzymatic activity in HBCSs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>Results showed that HIF\u20101\u03b1 inhibitor increased viability defect in the Dox\u2010resistant HBCSs. Interestingly, at higher Dox concentrations, chemoresistance was mitigated independently of HIF\u20101\u03b1 and promoted apoptosis and ROS accumulation, which were correlated with PK2 release.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications<\/jats:title>\n                    <jats:p>Our findings provide the first evidence that PK2 may serve as a predictive pharmacodynamic marker, offering a potential strategy to overcome drug resistance in targeted cancer therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70204","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T02:24:12Z","timestamp":1758507852000},"page":"491-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of prokineticin\u20102 as potential pharmacodynamic biomarker for overcoming doxorubicin resistance in multicellular breast cancer spheroids"],"prefix":"10.1111","volume":"183","author":[{"given":"Martina","family":"Vincenzi","sequence":"first","affiliation":[{"name":"Regenerative Nanomedicine (UMR 1260), INSERM University of Strasbourg, Center of Research in Biomedicine of Strasbourg  Strasbourg France"},{"name":"Department of Physiology and Pharmacology \u2018Vittorio Erspamer\u2019 Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin","family":"Kremic","sequence":"additional","affiliation":[{"name":"Regenerative Nanomedicine (UMR 1260), INSERM University of Strasbourg, Center of Research in Biomedicine of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie N.","family":"Tscheiller","sequence":"additional","affiliation":[{"name":"Regenerative Nanomedicine (UMR 1260), INSERM University of Strasbourg, Center of Research in Biomedicine of Strasbourg  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Yen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Regenerative Nanomedicine (UMR 1260), INSERM University of Strasbourg, Center of Research in Biomedicine of Strasbourg  Strasbourg France"},{"name":"Department of Biomedical Sciences National Chung Cheng University  Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W. 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