{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:47:29Z","timestamp":1773852449294,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite advances in the 5-year survival rates for prostate cancer patients, progression to metastatic castration-resistant prostate cancer (mCRPC) remains a significant challenge following standard treatments. Antibody-drug conjugates (ADCs) are an emerging class of biopharmaceuticals that combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs. Trophoblast cell surface antigen 2 (Trop-2) is overexpressed in prostate cancer, particularly in metastatic forms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Response to this, we developed a novel Trop-2-targeted antibody-drug conjugate (ADC), SHR-A1921, which incorporates a potent DNA topoisomerase I inhibitor,SHR9265. Its\n                      <jats:italic>in vitro<\/jats:italic>\n                      cytotoxicity was assessed across prostate cancer cell lines with differential Trop-2 expression. Subcutaneous xenograft models were established for\n                      <jats:italic>in vivo<\/jats:italic>\n                      tumor-suppressive activity evaluation, and patient-derived organoid models validated its potential clinical efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In preclinical models, SHR-A1921 specifically bound to Trop-2, followed by internalization into tumor cells and subsequent intracellular trafficking to lysosomes, where the release of SHR9265 occurred. This resulted in DNA damage and apoptosis in Trop-2-expressing tumor cells\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                      <jats:italic>In vivo<\/jats:italic>\n                      , SHR-A1921 exhibited significant antitumor activity, inducing DNA damage in Trop-2-positive xenograft tumors. Additionally, SHR-A1921 demonstrated antitumor effects in Trop-2-expressing prostate cancer organoids. Safety assessments in rats indicated that SHR-A1921 had an acceptable safety profile.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SHR-A1921 is a promising Trop-2-targeted ADC that leverages innovative technology to deliver potent antitumor activity against Trop-2-expressing prostate cancer cells, with an acceptable safety profile observed in preclinical studies. These results highlight the promising clinical potential of SHR-A1921 as a therapeutic option for prostate cancer patients with Trop-2-positive tumors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1713983","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T10:23:41Z","timestamp":1773829421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical activity of SHR-A1921, a novel antibody-drug conjugate targeting trophoblast cell-surface antigen2 (Trop-2) in prostate cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Binyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Institute of Urology, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuya","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Urology, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Institute of Urology, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Institute of Urology, Nanjing University","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongqian","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Institute of Urology, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Institute of Urology, Nanjing University","place":["Nanjing, Jiangsu, China"]},{"name":"Department of Urology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nrd.2016.268","article-title":"Strategies and challenges for the next generation of antibody-drug conjugates","volume":"16","author":"Beck","year":"2017","journal-title":"Nat. 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