中国科学院上海药物研究所Yong-zhuo Huang和滨州医学院附属医院Wen-wen Lv合作，近期取得重要工作进展。他们研究提出了脂质体共递送系统介导Osimertinib（Osi）和Panobinostat（Pan）的联合治疗策略，这一用药策略能够克服非小细胞癌症（NSCLC）对Osimertinib单独治疗产生的耐药性。相关研究成果2023年12月19日在线发表于《中国药理学学报》杂志上。

据介绍，Osi被广泛作为EGFR突变NSCLC的一线治疗药物。然而，大多数接受Osi治疗的患者最终在一年内复发。Osi耐药性产生的机制在很大程度上还不清楚。

研究人员开发了一种乳铁蛋白修饰的脂质体共递送系统，用于Osi和组蛋白乙酰化表观遗传调节因子Pan的联合治疗。研究人员证明，共递送脂质体可以有效地使肿瘤相关巨噬细胞（TAM）从M2表型重新极化到M1表型，逆转肿瘤细胞中上皮-间充质转化（EMT）相关的耐药性，并抑制糖酵解、乳酸产生和血管生成。

总之，这一研究结果表明，通过脂质体共递送系统介导的Osi和Pan的联合治疗，是克服NSCLC中Osi耐药性的一种有前景的策略。

附：英文原文

Title: Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages

Author: Lin, Ting-ting, Xiong, Wei, Chen, Gui-hua, He, Yang, Long, Li, Gao, Xin-fu, Zhou, Jia-lin, Lv, Wen-wen, Huang, Yong-zhuo

Issue&Volume: 2023-12-19

Abstract: Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.

DOI: 10.1038/s41401-023-01205-4

Source: https://www.nature.com/articles/s41401-023-01205-4