Camptothecin and its derivatives (CPTs) are potent antineoplastic agents that exert their effects by inhibiting DNA topoisomerase I, leading to apoptosis during cell proliferation. Since their discovery in the 1960s, CPTs have faced challenges such as low water solubility, pH-dependent lactone ring instability, and severe off-target toxicities. Despite extensive research, only two CPTs, irinotecan and topotecan, have received health authority approval. Ongoing clinical trials continue to explore the use of CPTs in combination with targeted therapies and immunotherapies to expand their clinical use. Drug delivery systems, including liposomes and antibody–drug conjugates (ADCs), have significantly enhanced the therapeutic index of CPTs. Liposomal irinotecan (Onivyde®, Ipsen, Paris, France) and two ADCs delivering CPT payloads, trastuzumab deruxtecan (Enhertu®, Daiichi Sankyo, Tokyo, Japan) and sacituzumab govitecan (Trodelvy®, Gilead Sciences, Inc., Foster City, CA, USA), have demonstrated substantial efficacy and safety. There is promise that novel strategies such as inverse targeting and co-dosing with anti-idiotypic distribution enhancers may expand the utility of CPT ADCs. This review highlights CPT therapies in clinical use and discusses approaches to further enhance their therapeutic selectivity.
喜树碱及其衍生物（CPTs）是一类强效抗肿瘤药物，通过抑制DNA拓扑异构酶I发挥作用，在细胞增殖过程中诱导细胞凋亡。自20世纪60年代被发现以来，CPTs一直面临水溶性低、内酯环稳定性受pH影响显著以及严重脱靶毒性等挑战。尽管已有大量研究，目前仅有伊立替康和拓扑替康两种CPTs获得卫生监管机构批准。正在进行的临床试验持续探索CPTs与靶向疗法及免疫疗法的联合应用，以拓展其临床适用范围。以脂质体和抗体药物偶联物（ADCs）为代表的药物递送系统显著提升了CPTs的治疗指数。脂质体伊立替康（Onivyde®，法国巴黎益普生公司）以及两种搭载CPTs有效载荷的ADCs——曲妥珠单抗德鲁替康（Enhertu®，日本东京第一三共株式会社）和戈沙妥珠单抗（Trodelvy®，美国加州福斯特城吉利德科学公司），均已展现出显著的疗效与安全性。逆向靶向策略及与抗独特型分布增强剂的联合给药等新型方案，有望进一步拓展CPT类ADCs的应用前景。本综述重点阐述临床应用的CPT疗法，并探讨进一步提升其治疗选择性的策略。
Camptothein-Based Anti-Cancer Therapies and Strategies to Improve Their Therapeutic Index
肿瘤(癌症)患者之家