Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that has become central to prostate cancer (PCa) diagnostics and treatment. Beyond its enzymatic role in folate and glutamate metabolism, PSMA is upregulated in advanced PCa, where it contributes to angiogenesis, tumour progression, and therapeutic resistance. This review integrates current understanding of PSMA biology with an emphasis on the role of PSMA expression and the hallmarks of cancer-proliferative signalling, metabolic adaptation, and evasion of cell death. While PSMA has revolutionised theranostic strategies in PCa, its utility as a sole biomarker is limited in select cases such as neuroendocrine differentiation and discordant disease biology. To address these challenges, we highlight emerging biomarkers and novel imaging markers that complement PSMA, including genomic alterations, circulating tumour markers, and exosomal microRNAs. Advances in radiomics and dual-tracer positron emission tomography (PET) further refine patient selection by capturing aggressive low-PSMA phenotypes. Furthermore, PSMA-PET is showing promise in other malignancies, including renal cell carcinoma (RCC) and glioblastoma multiforme (GBM), where neovasculature expression may extend its theranostic applications beyond PCa. By situating PSMA within this broader biomarker landscape, we outline opportunities for theranostic integration, including predictive models, combination therapies and expansion into non-prostate malignancies. Understanding the biology of PSMA in conjunction with novel biomarkers provides a framework for optimising theranostic applications and advancing personalised cancer care.
前列腺特异性膜抗原（PSMA）是一种Ⅱ型跨膜糖蛋白，已成为前列腺癌（PCa）诊断与治疗的核心靶点。除在叶酸和谷氨酸代谢中发挥酶活性作用外，PSMA在晚期前列腺癌中表达上调，参与血管生成、肿瘤进展及治疗抵抗过程。本综述整合当前对PSMA生物学功能的认识，重点探讨PSMA表达与癌症标志性特征——增殖信号传导、代谢适应及细胞死亡逃逸之间的关联。尽管PSMA已革新前列腺癌的诊疗一体化策略，但在神经内分泌分化及异质性肿瘤生物学等特定情况下，其作为单一生物标志物的应用存在局限。为应对这些挑战，我们重点阐述了与PSMA形成互补的新兴生物标志物及新型影像标志物，包括基因组变异、循环肿瘤标志物和外泌体微小RNA。影像组学与双示踪剂正电子发射断层扫描（PET）的技术进展，通过捕捉侵袭性低PSMA表型进一步优化了患者分层。此外，PSMA-PET在肾细胞癌（RCC）和多形性胶质母细胞瘤（GBM）等其他恶性肿瘤中也展现出应用潜力，其在新生命管系统的表达可能将诊疗一体化应用拓展至前列腺癌之外。通过将PSMA置于更广阔的肿瘤标志物谱系中审视，我们勾勒出诊疗一体化整合的发展方向，包括预测模型构建、联合治疗方案设计以及向非前列腺恶性肿瘤领域的拓展。结合新型生物标志物深入理解PSMA的生物学特性，将为优化诊疗一体化应用和推进个体化癌症治疗提供理论框架。
PSMA Theranostics in Prostate Cancer and Beyond: Current and Future Perspectives
肿瘤(癌症)患者之家