肿瘤细胞治疗研究
英文原题：Overcoming Therapy Resistance in Ovarian Cancer: From Molecular Mechanisms to Emerging Therapeutic Strategies.
背景/目的：上皮性卵巢癌（EOC）仍是一种预后较差的妇科恶性肿瘤，晚期疾病的5年生存率约为29%。
背景/目的：上皮性卵巢癌（EOC）仍是一种预后较差的妇科恶性肿瘤，晚期患者的5年生存率约为29%。尽管采用肿瘤细胞减灭术以及以铂类和紫杉烷类为基础的化疗，大多数患者仍在2年内复发。主要治疗障碍包括化疗耐药、分子异质性和免疫抑制性腹膜微环境。本综述总结了EOC新兴治疗策略、其作用机制以及克服治疗耐药的潜力。方法：检索PubMed/MEDLINE中针对新型卵巢癌疗法及耐药机制的临床前研究、I-III期临床试验、系统综述和荟萃分析。结果：本综述涵盖分子靶向治疗、免疫治疗、代谢和表观遗传学方法、细胞和基因治疗、靶向药物递送系统以及局部区域和物理治疗方式。策略包括PARP抑制剂、抗血管生成药物、抗体-药物偶联物、通路抑制剂、免疫检查点抑制剂、癌症疫苗、过继性细胞治疗、代谢和表观遗传调节剂、CAR-T、CAR-NK、CRISPR/Cas9、HIPEC、PIPAC、消融、光动力治疗和声动力治疗。结论：这些方法的临床成熟度差异很大。PARP抑制剂、抗血管生成药物、部分抗体-药物偶联物、LGSOC中的MAPK导向治疗以及特定情况下的HIPEC具有最强的临床支持。大多数免疫联合方案、代谢和表观遗传治疗、过继性细胞治疗、基因编辑方法以及新型递送或物理治疗方式仍处于早期临床阶段或主要为临床前阶段。进展将取决于生物标志物指导的患者选择、对不断演变的耐药机制的重新评估，以及合理的治疗顺序和联合方案。
Background/Objectives : Epithelial ovarian cancer (EOC) remains a gynecologic malignancy with a poor prognosis, with a 5-year survival of approximately 29% in advanced-stage disease. Despite cytoreductive surgery and platinum- and taxane-based chemotherapy, most patients relapse within 2 years. Major therapeutic barriers include chemoresistance, molecular heterogeneity, and an immunosuppressive peritoneal microenvironment. This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance. Methods : PubMed/MEDLINE was searched for preclinical studies, phase I-III clinical trials, systematic reviews, and meta-analyses addressing novel ovarian cancer therapies and resistance mechanisms. Results: The review covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities. Strategies include PARP inhibitors, antiangiogenic agents, antibody-drug conjugates, pathway inhibitors, immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies, metabolic and epigenetic modulators, CAR-T, CAR-NK, CRISPR/Cas9, HIPEC, PIPAC, ablation, photodynamic therapy, and sonodynamic therapy. Conclusions : The clinical maturity of these approaches varies substantially. PARP inhibitors, antiangiogenic agents, selected antibody-drug conjugates, MAPK-directed therapy in LGSOC, and HIPEC in selected settings have the strongest clinical support. Most immune combinations, metabolic and epigenetic therapies, adoptive cell therapies, gene-editing approaches, and novel delivery or physical modalities remain early clinical or predominantly preclinical. Progress will depend on biomarker-guided patient selection, reassessment of evolving resistance mechanisms, and rational treatment sequencing and combinations.
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