{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:19:53Z","timestamp":1765261193410,"version":"3.46.0"},"reference-count":53,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001787","name":"University of South Australia","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001787","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Envision Sciences Pty Ltd","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Cancer Council SA Beat Cancer Grant","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"NHMRC development grant","award":["GNT1092904"],"award-info":[{"award-number":["GNT1092904"]}]},{"name":"MTP Connect Biomedical Translation Bridge Program grant","award":["BTBR200074"],"award-info":[{"award-number":["BTBR200074"]}]},{"DOI":"10.13039\/501100000927","name":"Prostate Cancer Foundation of Australia","doi-asserted-by":"publisher","award":["PIRA FLMCR-1023"],"award-info":[{"award-number":["PIRA FLMCR-1023"]}],"id":[{"id":"10.13039\/501100000927","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite prostate cancer being one of the most common malignancies in men, its pathological diagnosis remains plagued by inter-observer variability and diagnostic ambiguity. Traditional morphological assessment and currently available biomarkers such as PSA (Prostate-Specific Antigen), AMACR (Alpha methylacyl CoA racemase), and p63 suffer from poor specificity and clinical reliability. In this review, we present a pathogenesis-guided biomarker discovery strategy that led to the development of a clinically validated biomarker panel\u2014Appl-1, Sortilin, and Syndecan-1. These biomarkers, which reflect fundamental biological processes within the endosome\u2013lysosome system, offer improved diagnostic precision and prognostic utility for patients with prostate cancer. This review discusses the rationale behind their discovery, the multidisciplinary approach that enabled it, the evidence supporting their use, and their implementation in U.S. clinical practice as a lab-developed test (LDT). We propose this approach as a new diagnostic standard that bridges mechanistic insight with real-world application.<\/jats:p>","DOI":"10.3390\/ijms262411786","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T15:11:24Z","timestamp":1764947484000},"page":"11786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-6908","authenticated-orcid":false,"given":"Jessica M.","family":"Logan","sequence":"first","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Malone","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland"},{"name":"Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7311-9326","authenticated-orcid":false,"given":"John J.","family":"O\u2019Leary","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland"},{"name":"Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9098-3626","authenticated-orcid":false,"given":"Doug A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia"},{"name":"Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","unstructured":"World Cancer Research Fund International (2024, July 22). 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