{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"American Association for Cancer Research"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T03:11:47Z","timestamp":1747192307071,"version":"3.40.5"},"posted":{"date-parts":[[2023,3,31]]},"reference-count":0,"publisher":"American Association for Cancer Research (AACR)","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<div>AbstractPurpose:<p>Neuroendocrine prostate cancer (NEPC) is an aggressive form of castration-resistant prostate cancer (CRPC) for which effective therapies are lacking. We previously identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a promising NEPC cell surface antigen. Here we investigated the scope of CEACAM5 expression in end-stage prostate cancer, the basis for CEACAM5 enrichment in NEPC, and the therapeutic potential of the CEACAM5 antibody\u2013drug conjugate labetuzumab govitecan in prostate cancer.<\/p>Experimental Design:<p>The expression of CEACAM5 and other clinically relevant antigens was characterized by multiplex immunofluorescence of a tissue microarray comprising metastatic tumors from 34 lethal metastatic CRPC (mCRPC) cases. A genetically defined neuroendocrine transdifferentiation assay of prostate cancer was developed to evaluate mechanisms of CEACAM5 regulation in NEPC. The specificity and efficacy of labetuzumab govitecan was determined in CEACAM5<sup>+<\/sup> prostate cancer cell lines and patient-derived xenografts models.<\/p>Results:<p>CEACAM5 expression was enriched in NEPC compared with other mCRPC subtypes and minimally overlapped with prostate-specific membrane antigen, prostate stem cell antigen, and trophoblast cell surface antigen 2 expression. We focused on a correlation between the expression of the pioneer transcription factor <i>ASCL1<\/i> and <i>CEACAM5<\/i> to determine that ASCL1 can drive neuroendocrine reprogramming of prostate cancer which is associated with increased chromatin accessibility of the <i>CEACAM5<\/i> core promoter and CEACAM5 expression. Labetuzumab govitecan induced DNA damage in CEACAM5<sup>+<\/sup> prostate cancer cell lines and marked antitumor responses in CEACAM5<sup>+<\/sup> CRPC xenograft models including chemotherapy-resistant NEPC.<\/p>Conclusions:<p>Our findings provide insights into the scope and regulation of CEACAM5 expression in prostate cancer and strong support for clinical studies of labetuzumab govitecan for NEPC.<\/p><\/div><\/jats:p>","DOI":"10.1158\/1078-0432.c.6530156","type":"posted-content","created":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T08:54:08Z","timestamp":1680339248000},"source":"Crossref","is-referenced-by-count":0,"title":["Data from Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5\u2013SN38 Antibody\u2013drug Conjugate in Neuroendocrine Prostate Cancer"],"prefix":"10.1158","author":[{"given":"Diana C.","family":"DeLucia","sequence":"first","affiliation":[]},{"given":"Thomas M.","family":"Cardillo","sequence":"first","affiliation":[]},{"given":"Lisa","family":"Ang","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7887-7599","authenticated-orcid":false,"given":"Mark P.","family":"Labrecque","sequence":"first","affiliation":[]},{"given":"Ailin","family":"Zhang","sequence":"first","affiliation":[]},{"given":"James E.","family":"Hopkins","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2139-7951","authenticated-orcid":false,"given":"Navonil","family":"De Sarkar","sequence":"first","affiliation":[]},{"given":"Ilsa","family":"Coleman","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2151-2449","authenticated-orcid":false,"given":"Rui M. Gil","family":"da Costa","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9244-3807","authenticated-orcid":false,"given":"Eva","family":"Corey","sequence":"first","affiliation":[]},{"given":"Lawrence D.","family":"True","sequence":"first","affiliation":[]},{"given":"Michael C.","family":"Haffner","sequence":"first","affiliation":[]},{"given":"Michael T.","family":"Schweizer","sequence":"first","affiliation":[]},{"given":"Colm","family":"Morrissey","sequence":"first","affiliation":[]},{"given":"Peter S.","family":"Nelson","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-2180","authenticated-orcid":false,"given":"John K.","family":"Lee","sequence":"first","affiliation":[]}],"member":"1086","container-title":[],"original-title":[],"deposited":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T08:54:08Z","timestamp":1680339248000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacr.figshare.com\/collections\/Data_from_Regulation_of_CEACAM5_and_Therapeutic_Efficacy_of_an_Anti-CEACAM5_SN38_Antibody_drug_Conjugate_in_Neuroendocrine_Prostate_Cancer\/6530156"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1158\/1078-0432.c.6530156","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1158\/1078-0432.CCR-20-3396","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,3,31]]},"subtype":"other"}}