Advanced prostate cancer, particularly castration-resistant disease, remains challenging to treat due to intratumoral heterogeneity, immune exclusion, and a suppressive tumor microenvironment. Within this ecosystem, cancer-associated fibroblasts shape tumor–stroma communication, but their marked heterogeneity and plasticity complicate classification and make indiscriminate fibroblast depletion potentially ineffective or even harmful. This review summarizes recent progress in fibroblast origins, functional subtypes, and fibroblast-driven mechanisms that promote tumor progression and therapy resistance, as well as emerging therapeutic opportunities in prostate cancer. We conducted a structured literature search of PubMed, ScienceDirect, and major publisher platforms (including Nature and SpringerLink) from database inception to 15 February 2025, supplemented by targeted manual screening of reference lists. Evidence from single-cell/spatial-omics and mechanistic studies indicates that prostate tumors contain multiple fibroblast programs that occupy distinct niches yet can interconvert. Across these studies, it was found that these fibroblasts contribute to immune suppression, extracellular matrix remodeling and stromal barrier formation, angiogenesis, and metabolic support, collectively limiting drug penetration and reinforcing immune evasion; therapeutic pressure can further rewire fibroblast states and resistance-associated signaling. Overall, the literature supports a shift toward function- and subtype-directed intervention rather than “one-size-fits-all” targeting, with promising directions including precision targeting and reversible reprogramming, rational combination strategies, and localized delivery approaches that reduce stromal barriers while preserving tissue homeostasis in high-risk and treatment-refractory prostate cancer.
晚期前列腺癌，尤其是去势抵抗性疾病，由于肿瘤内异质性、免疫排斥及抑制性肿瘤微环境等因素，治疗仍面临挑战。在这一生态系统中，癌相关成纤维细胞塑造了肿瘤-间质间的信息交流，但其显著的异质性和可塑性使得分类复杂化，不加区分地清除成纤维细胞可能效果有限甚至有害。本综述总结了成纤维细胞的起源、功能亚型及其驱动肿瘤进展和治疗抵抗机制的最新研究进展，以及前列腺癌领域新兴的治疗机遇。我们系统检索了从数据库建立至2025年2月15日期间PubMed、ScienceDirect及主要出版平台（包括Nature和SpringerLink）的文献，并辅以对参考文献列表的定向人工筛查。单细胞/空间组学及机制研究证据表明，前列腺肿瘤包含多种成纤维细胞程序，这些程序占据不同的生态位且可相互转化。综合研究发现，这些成纤维细胞参与免疫抑制、细胞外基质重塑与间质屏障形成、血管生成及代谢支持，共同限制药物渗透并强化免疫逃逸；治疗压力可进一步重构成纤维细胞状态及耐药相关信号传导。总体而言，现有文献支持从“一刀切”靶向治疗转向功能与亚型导向的干预策略，包括精准靶向与可逆重编程、合理联合治疗策略以及局部递送方法等前景方向，这些策略可在降低间质屏障的同时，维持高危和治疗难治性前列腺癌的组织稳态。
肿瘤(癌症)患者之家