{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:25:13Z","timestamp":1783445113004,"version":"3.54.6"},"reference-count":120,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Center","award":["2211880-3"],"award-info":[{"award-number":["2211880-3"]}]},{"name":"National Cancer Center","award":["1941760-1"],"award-info":[{"award-number":["1941760-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, and comprise distinct functional states with divergent effects on disease progression, immune regulation, and therapeutic resistance. To bridge this gap, we synthesize evidence from single-cell and spatial transcriptomic studies, tissue-based pathology, liquid biopsy assays, and molecular imaging to construct an evidence-tiered, decision-oriented translational framework that connects stromal mechanisms, translational measurement strategies, and therapeutic interventions in PCa. Single-cell and spatial transcriptomic analyses have consistently identified multiple CAF programs, including matrix-remodeling, inflammatory, immunoregulatory, antigen-presenting, and therapy-imprinted states, each with distinct functional outputs and clinical correlates. Tissue-based readouts, including reactive stromal grade (RSG) and fibroblast activation protein (FAP) immunohistochemistry, provide practical proxies for stromal activation and correlate with disease-specific mortality and imaging phenotypes. Circulating CAFs (cCAFs) represent an emerging liquid biopsy modality for longitudinal stromal monitoring, although technical standardization is required before clinical implementation. FAP-targeted PET imaging and emerging dual prostate-specific membrane antigen (PSMA)\/FAP-targeted theranostic strategies provide noninvasive tools for patient selection and response assessment, particularly in PSMA-discordant or tracer-heterogeneous disease. Androgen receptor (AR)-targeted therapy can reprogram stromal states toward resistance-promoting circuits, highlighting the dynamic and plastic nature of the CAF compartment. A state-based CAF framework organizes stromal biology into testable translational hypotheses rather than immediate clinical standards. RSG and FAP-based tissue or imaging readouts are practical markers of stromal activation, whereas spatial CAF-immune signatures and cCAF assays remain investigational and require assay harmonization and prospective validation. Future trials should pre-specify stromal biomarkers as enrichment or pharmacodynamic variables when matched to the intervention and should avoid treating CAFs as a uniform therapeutic target.<\/jats:p>","DOI":"10.3390\/cancers18101600","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:04:09Z","timestamp":1778763849000},"page":"1600","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering the Heterogeneity of Cancer-Associated Fibroblasts in Prostate Cancer: From Stromal Biology to Clinical Translation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0883-9075","authenticated-orcid":false,"given":"Ho Trong Tan","family":"Truong","sequence":"first","affiliation":[{"name":"Department of Urology, Cho Ray Hospital, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-5981","authenticated-orcid":false,"given":"Whi-An","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University College of Medicine, Myongji Hospital, Goyang 10475, Republic of Korea"},{"name":"Research Institute of Precision Medicine and Geroscience, Myongji Medical Foundation, Goyang 10475, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeong Jung","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of New Biology, DGIST, Techno Jungang-Daero 333, Daegu 42988, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minseok S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of New Biology, DGIST, Techno Jungang-Daero 333, Daegu 42988, Republic of Korea"},{"name":"CTCELLS Inc., Seoul 06307, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3529-1760","authenticated-orcid":false,"given":"Nhu Quang","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Urology, Cho Ray Hospital, Ho Chi Minh City 700000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Young","family":"Joung","sequence":"additional","affiliation":[{"name":"Department of Urology, Urological Cancer Center, National Cancer Center, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.canlet.2015.12.022","article-title":"Regulation of prostate cancer progression by the tumor microenvironment","volume":"380","author":"Shiao","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nrc.2016.73","article-title":"The biology and function of fibroblasts in cancer","volume":"16","author":"Kalluri","year":"2016","journal-title":"Nat. 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