{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T11:54:39Z","timestamp":1781610879990,"version":"3.54.5"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012681","name":"Universit\u00e4tsklinikum K\u00f6ln","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012681","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["World J Urol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the expression of trophoblast cell surface antigen-2 (TROP-2), a broadly expressed antibody-drug conjugate (ADC) target, in non-clear cell renal cell carcinoma (nccRCC), and to perform a proof-of-concept analysis assessing the cytotoxic efficacy of the TROP-2-directed ADC Sacituzumab govitecan (SG) in RCC cell lines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cohort comprising clear cell RCC (ccRCC,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200944), papillary (pRCC,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922), chromophobe (chRCC,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922), and benign renal tumors (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098, including oncocytoma and angiomyolipoma) was analysed using reverse transcription quantitative PCR (RT-qPCR), immunohistochemistry (IHC) with H-score quantification, and enzyme-linked immunosorbent assay (ELISA). In RCC cell lines, TROP-2 protein levels were assessed by Western blotting and flow cytometry, and SG cytotoxicity was evaluated using MTT assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TROP-2 mRNA levels were significantly elevated in pRCC compared to ccRCC, chRCC and benign renal tumors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). IHC revealed moderate to strong membranous TROP-2 expression in most pRCC cases [\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920\/22 with H-score\u2009\u2265\u2009100, median H-score 265 (IQR 202.5\u2013290)], while TROP-2 expression was absent or weak in ccRCC and chRCC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Soluble TROP-2 was detectable in patient serum of RCC patients and strongly correlated with tissue expression (\u03c1\u2009=\u20090.78,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001, R\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.52). In vitro, TROP-2-positive Caki-1 cells exhibited significant growth inhibition after SG treatment, whereas TROP-2-negative 769-P cells showed resistance (\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>The selective overexpression of TROP-2 in pRCC, and its functional relevance demonstrated in vitro, provide compelling preclinical evidence supporting TROP-2 as a therapeutic target. These findings support further investigation of TROP-2-directed ADCs, such as SG, in patients with metastatic TROP-2-positive pRCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00345-025-05880-2","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T11:26:43Z","timestamp":1756726003000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TROP-2 overexpression in papillary renal cell carcinoma supports its potential as a therapeutic target for antibody-drug-conjugate therapy"],"prefix":"10.1007","volume":"43","author":[{"given":"Carolina","family":"Kessler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"von Brandenstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Kl\u00fcmper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Krausewitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enno","family":"Storz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurenz","family":"Sperber","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":"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":[[2025,9,1]]},"reference":[{"issue":"8","key":"5880_CR1","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/j.annonc.2024.05.537","volume":"35","author":"T Powles","year":"2024","unstructured":"Powles T et al (2024) Renal cell carcinoma: ESMO clinical practice guideline for diagnosis, treatment and follow-up <\u2009sup>\u2606. 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PK: Personal fees, travel costs, and speaker\u2019s honoraria from Bayer, Janssen-Cilag, Medac. ME: Personal fees, travel costs and speaker\u2019s honoraria from MSD, AstraZeneca, Janssen-Cilag, Cepheid, Roche, Astellas, Diaceutics; research funding from AstraZeneca, Janssen-Cilag, STRATIFYER, Cepheid, Roche, Gilead; advisory roles for Diaceutics, MSD, AstraZeneca, Janssen-Cilag, GenomicHealth. 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