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There is a clear unmet need for new therapies in this setting. Antibody\u2013drug conjugates (ADCs) have emerged as a promising class of targeted agents for chemoresistant solid tumors. This study aimed to evaluate the expression of TROP2 in cisplatin-resistant GCT metastases [MET(-R)] and to assess the cytotoxic efficacy of the anti-TROP2 ADC sacituzumab govitecan (SG) in GCT cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TROP2 mRNA and protein expression levels were analyzed in 31 post-chemotherapy viable MET(-R) specimens, including embryonal carcinoma (EC), choriocarcinoma (CC), yolk sac tumor (YST), and teratoma (TER), using quantitative reverse transcription polymerase chain reaction and immunohistochemistry with H-score evaluation. In vitro analyses included Western blotting and cell viability assays to assess TROP2 protein expression and SG-mediated cytotoxicity in GCT cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TROP2<\/jats:italic>\n                      mRNA expression was significantly higher in post-chemotherapy CC- and TER-MET(-R) compared to YST-MET(-R) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Immunohistochemistry showed moderate to strong membranous TROP2 expression in CC-MET(-R) [with H-score\u2009\u2265\u2009100, median H-score 280 (interquartile range, IQR 225.0\u2013298.0)] and TER-MET(-R) [median H-score 255 (IQR 200.0\u2013265.0)]. Conversely, EC- and YST-MET(-R) showed absent or weak TROP2 expression [EC median H-score 22.5 (IQR 5.0\u201373.8); YST median H-score 0 (IQR 0\u201312.5)]. In vitro, SG induces dose-dependent cytotoxicity in TROP2-positive GCT cells, including cisplatin-resistant subclones (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, TROP2 is variably expressed in cisplatin-resistant metastatic GCTs, with high expression most often seen in CC. SG shows strong cytotoxicity in TROP2-positive, chemotherapy-resistant GCT cells; however, its clinical effectiveness still needs to be confirmed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-025-06325-4","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T03:19:33Z","timestamp":1759807173000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression and therapeutic potential of TROP2 in cisplatin-resistant germ cell tumors"],"prefix":"10.1007","volume":"151","author":[{"given":"Laurenz","family":"Sperber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"von Brandenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Kessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Heidenreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enno","family":"Storz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pfister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Paffenholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Tolkach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit","family":"Bernhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph","family":"Wirtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Eckstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Heidenreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7216-1033","authenticated-orcid":false,"given":"Richard","family":"Weiten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"issue":"16","key":"6325_CR1","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1056\/NEJMoa2028485","volume":"384","author":"A Bardia","year":"2021","unstructured":"Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cort\u00e9s J, O\u2019Shaughnessy J, Di\u00e9ras V, Rugo HS (2021a) Sacituzumab govitecan in metastatic triple-negative breast cancer. 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All other authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Ethics Committee of the Medical Faculty of the University of Cologne (approval number: 23-1178) and conducted in accordance with the principles outlined in the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients provided written informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"During the preparation of this work, the authors used ChatGPT (OpenAI) to improve the readability and language of the manuscript. After using this tool, they reviewed and edited the content as needed and assume full responsibility for the publication's content.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}}],"article-number":"279"}}