{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:13:50Z","timestamp":1788146030047,"version":"build-2803163510"},"reference-count":149,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Liquid biopsy enables minimally invasive detection and longitudinal monitoring of tumor-derived material in blood and urine. In genitourinary cancers, most applications have focused on genomic alterations in circulating tumor DNA (ctDNA), together with circulating tumor cells (CTCs), extracellular vesicles (EVs), and cell-free RNAs. These measurements are clinically informative but are often interpreted as isolated, predominantly descriptive biomarkers and therefore incompletely represent the adaptive processes that determine progression and treatment response. We propose circulating tumor function (CTF) as a systems biology framework for integrating tumor-derived and host-derived genomic, regulatory, metabolic, redox, and immune signals obtained through serial liquid biopsy. CTF is not a single analyte or assay; rather, it is an inference model intended to generate interpretable functional states, including proliferative activity, immune evasion, metastatic potential, metabolic stress, and therapeutic adaptation. We review the contributions and limitations of ctDNA, ncRNA networks, EV-mediated signaling, redox biomarkers, and tumor\u2013host crosstalk in prostate, bladder, renal, and testicular cancers. We also outline the analytical and clinical validation required to determine whether integrated CTF models provide incremental value over established single-analyte approaches. This framework may help reposition liquid biopsy from molecular detection toward functional precision oncology.<\/jats:p>","DOI":"10.3390\/genes17091035","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Tumor Function: A Systems Biology Framework for Liquid Biopsy in Genitourinary Cancers"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-388X","authenticated-orcid":false,"given":"Roxana Andra","family":"Coman","sequence":"first","affiliation":[{"name":"Department of Fundamental Discipline, Anatomy, Faculty of Nursing and Health Sciences, Iuliu-Hatieganu University of Medicine and Pharmacy, Victor Babes Street Number 8, 400347 Cluj-Napoca, Romania"},{"name":"Department of Urology, MedLife Humanitas Hospital, 400664 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-0903","authenticated-orcid":false,"given":"Andreea","family":"Nutu","sequence":"additional","affiliation":[{"name":"Genomics Department, MEDFUTURE Institute of Biomedical Research, Iuliu-Hatieganu University of Medicine and Pharmacy, 400336 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7793-4408","authenticated-orcid":false,"given":"Lia-Raluca","family":"Olari","sequence":"additional","affiliation":[{"name":"Genomics Department, MEDFUTURE Institute of Biomedical Research, Iuliu-Hatieganu University of Medicine and Pharmacy, 400336 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-0223","authenticated-orcid":false,"given":"Stefan","family":"Strilciuc","sequence":"additional","affiliation":[{"name":"Genomics Department, MEDFUTURE Institute of Biomedical Research, Iuliu-Hatieganu University of Medicine and Pharmacy, 400336 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7523-4747","authenticated-orcid":false,"given":"Dana Monica","family":"Iancu","sequence":"additional","affiliation":[{"name":"Department of Fundamental Discipline, Anatomy, Faculty of Nursing and Health Sciences, Iuliu-Hatieganu University of Medicine and Pharmacy, Victor Babes Street Number 8, 400347 Cluj-Napoca, Romania"},{"name":"Regional Institute of Gastroenterology and Hepatology \u201cOctavian Fodor\u201d, 19\u201321 Croitorilor Street, 400162 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-1325","authenticated-orcid":false,"given":"Ioana","family":"Berindan-Neagoe","sequence":"additional","affiliation":[{"name":"Genomics Department, MEDFUTURE Institute of Biomedical Research, Iuliu-Hatieganu University of Medicine and Pharmacy, 400336 Cluj-Napoca, Romania"},{"name":"Doctoral School, Iuliu-Hatieganu University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"},{"name":"Academy of Medical Sciences, 030171 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaay9040","DOI":"10.1126\/science.aay9040","article-title":"Early detection of cancer","volume":"375","author":"Crosby","year":"2022","journal-title":"Science"},{"key":"ref_2","first-page":"11","article-title":"Cancer diagnosis: From tumor to liquid biopsy and beyond","volume":"19","author":"Vaidyanathan","year":"2018","journal-title":"Lab Chip"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e481114","DOI":"10.1200\/EDBK-25-481114","article-title":"Liquid Biopsy Approaches for Cancer Characterization, Residual Disease Detection, and Therapy Monitoring","volume":"45","author":"Aredo","year":"2025","journal-title":"Am. 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