PDF(Pubmed)
Abstract：
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, including abemaciclib, have been approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced, and metastatic breast cancer. Despite the high therapeutic efficacy of CDK4/6 inhibitors, they are associated with various adverse effects, including potentially fatal interstitial lung disease. Therefore, a combination of CDK4/6 inhibitors with letrozole or fulvestrant has been attempted but has demonstrated limitations in reducing adverse effects, highlighting the need to develop new combination therapies. This study proposes a combination strategy using CDK4/6 inhibitors and tricyclic antidepressants to enhance the therapeutic outcomes of these inhibitors while reducing their side effects. The therapeutic efficacies of abemaciclib and desipramine were tested in different cancer cell lines (H460, MCF7, and HCT-116). The antitumor effects of the combined abemaciclib and desipramine treatment were evaluated in a xenograft colon tumor model. In vitro cell studies have shown the synergistic anticancer effects of combination therapy in the HCT-116 cell line. The combination treatment significantly reduced tumor size compared with control or single treatment without causing apparent toxicity to normal tissues. Although additional in vivo studies are necessary, this study suggests that the combination therapy of abemaciclib and desipramine may represent a novel therapeutic approach for treating solid tumors.
摘要：
细胞周期蛋白依赖性激酶4和6（CDK4/6）抑制剂，包括abemaciclib,已被批准用于治疗激素受体阳性，人表皮生长因子受体2（HER2）阴性晚期，和转移性乳腺癌。尽管CDK4/6抑制剂具有很高的治疗效果，它们与各种不利影响有关，包括潜在致命的间质性肺病.因此,已尝试将CDK4/6抑制剂与来曲唑或氟维司群联合使用，但已证明在减少不良反应方面存在局限性。强调需要开发新的联合疗法。这项研究提出了使用CDK4/6抑制剂和三环抗抑郁药的组合策略，以增强这些抑制剂的治疗效果，同时减少其副作用。在不同的癌细胞系（H460，MCF7和HCT-116）中测试了abemaciclib和地昔帕明的治疗效果。在异种移植结肠肿瘤模型中评估了abemaciclib和地昔帕明联合治疗的抗肿瘤作用。体外细胞研究显示了联合治疗在HCT-116细胞系中的协同抗癌作用。与对照或单一治疗相比,组合治疗显著减小了肿瘤大小,而不引起对正常组织的明显毒性。虽然额外的体内研究是必要的，这项研究表明，abemaciclib和地昔帕明的联合治疗可能是治疗实体瘤的一种新的治疗方法。
