Fu Shouyong, Li Changfei
Medical Device Department, Qingdao Hospital of University of Health and Rehabilitation Sciences, Qingdao, China.
Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, China.
Front Oncol. 2025 Sep 10;15:1661889. doi: 10.3389/fonc.2025.1661889. eCollection 2025.
Uveal melanoma (UM), the most common primary intraocular malignancy in adults, presents significant clinical challenges due to its high metastatic potential, pronounced hepatic tropism, and poor prognosis upon systemic dissemination. Despite established local therapies, nearly half of patients develop distant metastases, highlighting an urgent need for more effective systemic strategies. Recent advances in single-cell omics technologies (e.g., scRNA-seq, scATAC-seq, spatial transcriptomics) have revolutionized our understanding of UM pathobiology. These approaches have meticulously delineated the complex tumor heterogeneity, immunosuppressive microenvironment, and key molecular drivers-including novel macrophage subsets (e.g., immunosuppressive MΦ-C4), senescent endothelial cells, and non-canonical immune checkpoint expression-providing unprecedented resolution for identifying actionable therapeutic targets. Concurrently, innovations in materials science and biomedical engineering offer transformative opportunities for precision therapy. Engineered nanocarriers, biodegradable implants, and advanced gene therapy vectors (e.g., tropism-enhanced AAVs, CRISPR-Cas9 systems) enabled targeted drug delivery, sustained release, and genetic modulation tailored to the eye's unique anatomy and immune privilege. This review synthesizes these converging frontiers, outlining how the integration of multi-omics insights with smart biomaterials can overcome current therapeutic limitations. We catalog emerging material-based platforms applicable to UM and summarize validated molecular targets (e.g., GNAQ/GNA11, YAP/TAZ, BAP1, c-Met, CXCR4). Furthermore, we propose an interdisciplinary paradigm spanning combinatorial targeted therapies, immunomodulation, minimally invasive devices (e.g., robotic radiosurgery), and engineered delivery systems. By bridging mechanistic discovery with translational engineering, this synergy holds significant promise for advancing precision medicine and improving clinical outcomes in UM, ultimately facilitating the transition from bench to bedside.
葡萄膜黑色素瘤（UM）是成人中最常见的原发性眼内恶性肿瘤，因其高转移潜能、明显的肝嗜性以及全身播散后的不良预后而带来重大临床挑战。尽管已有成熟的局部治疗方法，但仍有近一半的患者发生远处转移，这凸显了对更有效的全身治疗策略的迫切需求。单细胞组学技术（如scRNA-seq、scATAC-seq、空间转录组学）的最新进展彻底改变了我们对UM病理生物学的理解。这些方法精心描绘了复杂的肿瘤异质性、免疫抑制微环境以及关键分子驱动因素，包括新型巨噬细胞亚群（如免疫抑制性MΦ-C4）、衰老内皮细胞和非经典免疫检查点表达，为识别可操作的治疗靶点提供了前所未有的分辨率。同时，材料科学和生物医学工程的创新为精准治疗提供了变革性机遇。工程纳米载体、可生物降解植入物和先进的基因治疗载体（如嗜性增强的腺相关病毒、CRISPR-Cas9系统）实现了针对眼部独特解剖结构和免疫赦免特性的靶向药物递送、持续释放和基因调控。本综述综合了这些汇聚的前沿领域，概述了多组学见解与智能生物材料的整合如何克服当前的治疗局限性。我们列举了适用于UM的新兴基于材料的平台，并总结了已验证的分子靶点（如GNAQ/GNA11、YAP/TAZ、BAP1、c-Met、CXCR4）。此外，我们提出了一种跨学科范式，涵盖联合靶向治疗、免疫调节、微创设备（如机器人放射外科）和工程递送系统。通过将机制发现与转化工程相结合，这种协同作用在推进精准医学和改善UM临床结果方面具有巨大潜力，最终促进从实验室到临床的转化。
