肿瘤细胞治疗研究
英文原题：Folate receptor-α targeted therapies in ovarian cancer: recent advances and emerging therapeutic strategies.
上皮性卵巢癌（EOC）仍是一种生物学异质性高、治疗困难的恶性肿瘤，因为大多数晚期肿瘤最初对铂类-紫杉烷化疗有应答，但随后复发，且铂类敏感性逐渐降低。
上皮性卵巢癌（EOC）具有生物学异质性且治疗困难；多数晚期肿瘤起初对铂类-紫杉烷化疗应答，之后却会复发并逐渐降低对铂类的敏感性。叶酸受体α（FRα/FOLR1）已成为精准肿瘤学中具有临床意义的靶点，因为其在高级别浆液性卵巢癌中富集，在许多极化正常上皮组织中相对不易接触循环药物，并且在配体或抗体结合后发生受体介导的内吞。本综述批判性评估FRα的作用，不仅将其视为叶酸转运蛋白，也将其视为生物标志物、递送入口、免疫靶点及耐药相关治疗轴。修订稿扩展了定量临床讨论，包括PARP抑制剂维持治疗、抗血管生成策略、免疫检查点阻断及FRα靶向抗体-药物偶联物的获益幅度和局限。Mirvetuximab soravtansine被列为当前临床基准，因为其在FRα阳性铂类耐药卵巢癌中已证实优于化疗；相比之下，早期裸抗体、叶酸-药物偶联物、肽疫苗和第一代CAR-T细胞虽显示生物学可行性，但未能持续带来持久生存获益。扩展讨论整合了抗原密度、上皮极性、内吞/再循环、旁观者载荷释放、眼部毒性、P-糖蛋白外排、微管蛋白载荷耐药、肿瘤相关巨噬细胞、调节性T细胞、HLA限制、生物标志物变异及病灶层面的靶点异质性。文章还讨论eribulin类ADC、IgE抗体、FRα靶向光动力治疗、PET/SPECT成像、叶酸纳米颗粒、放射性配体及合理联合等新兴策略，并将其视为基于机制的拓展，而非泛化附加方案。总体而言，卵巢癌FRα靶向治疗应被视为一种依据生物标志物调整的平台，需要标准化检测、定量药理学、毒性缓解及充分考虑耐药的试验设计。
Epithelial ovarian cancer (EOC) remains a biologically heterogeneous and therapeutically difficult malignancy because most advanced-stage tumors initially respond to platinum-taxane chemotherapy but later recur with progressively reduced platinum sensitivity. Folate receptor-alpha (FR /FOLR1) has become a clinically relevant precision-oncology target because it is enriched in high-grade serous ovarian carcinoma, is relatively shielded from circulating drugs in many polarized normal epithelia, and undergoes receptor-mediated internalization after ligand or antibody binding. This review critically evaluates FR not merely as a folate transporter but as a biomarker, delivery portal, immune target and resistance-associated therapeutic axis. The revised manuscript expands the quantitative clinical discussion, including the magnitude and limits of benefit from PARP inhibitor maintenance, anti-angiogenic strategies, immune-checkpoint blockade and FR -directed antibody-drug conjugates. Mirvetuximab soravtansine is positioned as the current clinical benchmark because it has demonstrated superiority over chemotherapy in FR -positive platinum-resistant ovarian cancer, while earlier naked antibodies, folate-drug conjugates, peptide vaccines and first-generation CAR-T cells have shown biological feasibility without consistently durable survival benefit. The expanded discussion integrates antigen density, epithelial polarity, endocytosis/recycling, bystander payload release, ocular toxicity, P-glycoprotein efflux, tubulin-payload resistance, tumor-associated macrophages, regulatory T cells, HLA restriction, biomarker variability and lesion-level target heterogeneity. Emerging strategies such as eribulin-based ADCs, IgE antibodies, FR -targeted photodynamic therapy, PET/SPECT imaging, folate nanoparticles, radioligands and rational combinations are discussed as mechanism-led extensions rather than generic additions. Overall, FR -targeted therapy in ovarian cancer is best understood as a biomarker-adapted platform that requires standardized testing, quantitative pharmacology, toxicity mitigation and resistance-aware trial design.
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