Gabizon Alberto A, Gabizon-Peretz Shira, Modaresahmadi Shadan, La-Beck Ninh M
The Leah and Jakub Susskind Nano-Oncology Research Laboratory, Helmsley Cancer Center, Shaare Zedek Medical Center, Jerusalem, Israel.
Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel.
BMJ Oncol. 2025 Jan 9;4(1):e000573. doi: 10.1136/bmjonc-2024-000573. eCollection 2025.
In 2025, it will be 30 years since the initial clinical approval of pegylated liposomal doxorubicin (PLD) by the Food and Drug Administration. PLD predated the field of nanomedicine and became a model nanomedicine setting key pharmacological principles (prolonged circulation, slow drug release and the enhanced permeability and retention (EPR) effect) for clinical application of other nano-drugs in cancer therapy. The impressive reduction of cardiotoxicity conferred by PLD is the most valuable clinical asset. While PLD has gained a strong foothold in relapsed ovarian cancer and metastatic breast cancer, it has not been extensively tested in primary (neoadjuvant) and adjuvant therapy and has not fulfilled the expectations from the results in animal models efficacy-wise. This discrepancy may be due to the large dose gap between mice and humans and the apparent variability of the EPR effect in human cancer. PLD is a complex product and we are still in a learning curve regarding a number of factors such as its interaction with the complement system and its immune modulatory properties, as well as its integration in multimodality therapy that may potentiate its value and role in cancer therapy.
到2025年，聚乙二醇化脂质体阿霉素（PLD）获得美国食品药品监督管理局的首次临床批准将满30年。PLD早于纳米医学领域出现，并成为纳米医学的一个典范，为其他纳米药物在癌症治疗中的临床应用确立了关键的药理学原理（延长循环时间、缓慢释放药物以及增强的渗透和滞留（EPR）效应）。PLD所带来的心脏毒性显著降低是其最有价值的临床优势。虽然PLD在复发性卵巢癌和转移性乳腺癌治疗中已站稳脚跟，但它尚未在原发性（新辅助）和辅助治疗中得到广泛测试，在疗效方面也未达到动物模型实验结果所带来的预期。这种差异可能是由于小鼠和人类之间的剂量差距巨大，以及人类癌症中EPR效应明显的变异性。PLD是一种复杂的产品，在许多因素方面我们仍处于学习阶段，比如它与补体系统的相互作用及其免疫调节特性，以及它在多模态治疗中的整合，这可能会增强其在癌症治疗中的价值和作用。
